query: at what point in the cell cycle does dna replication occur

pos: Cell cycle within interphase, from the end of the previous M phase until the beginning of DNA synthesis, is called G (G indicating "gap"). It is also called the growth phase. During this phase, the biosynthetic activities of the cell, which are considerably slowed down during M phase, resume at a high rate. The duration of G is highly variable, even among different cells of the same species. In this phase, the cell increases its supply of proteins, increases the number of organelles (such as mitochondria, ribosomes), and grows in size. In G phase, a cell has three options. (1) To continue

pos: DNA re-replication and Cdc6 expression. Loss of p53 regulation in cells can also be observed frequently in cell lines that overexpress Cdt1 or Cdc6. For the special case of cell cycle-regulated DNA replication in which DNA synthesis is uncoupled from cell cycle progression refer to endoreduplication. Endoreduplication is an important and widespread mechanism in many cell types. It does not adhere to many of the cell cycle checkpoints and damage controls in regularly dividing cells, but it does not result in uncontrolled re-replication. Endoreduplication is a controlled process and occurs to perform a specific cell function. In some cells, it has been

pos: Cyclin A makes chromatin capable of replication. When the amount of cyclin A/CDK2 complex reaches a threshold level, it terminates the assembly of the pre-replication complex made by cyclin E/CDK2. As the amount of Cyclin A/CDK2 complex increases, the complex initiates DNA replication. Cyclin A has a second function in S phase. In addition to initiating DNA synthesis, Cyclin A ensures that DNA is replicated once per cell cycle by preventing the assembly of additional replication complexes. This is thought to occur through the phosphorylation of particular DNA replication machinery components, such as CDC6, by the cyclin A/CDK2 complex. Since the action

pos: DNA replication the cell cycle; DNA replication takes place during the S phase (synthesis phase). The progress of the eukaryotic cell through the cycle is controlled by cell cycle checkpoints. Progression through checkpoints is controlled through complex interactions between various proteins, including cyclins and cyclin-dependent kinases. Unlike bacteria, eukaryotic DNA replicates in the confines of the nucleus. The G1/S checkpoint (or restriction checkpoint) regulates whether eukaryotic cells enter the process of DNA replication and subsequent division. Cells that do not proceed through this checkpoint remain in the G0 stage and do not replicate their DNA. Replication of chloroplast and mitochondrial genomes occurs

pos: Eukaryotic DNA replication errors. In G phase of the cell cycle, many of the DNA replication regulatory processes are initiated. In eukaryotes, the vast majority of DNA synthesis occurs during S phase of the cell cycle, and the entire genome must be unwound and duplicated to form two daughter copies. During G, any damaged DNA or replication errors are corrected. Finally, one copy of the genomes is segregated to each daughter cell at mitosis or M phase. These daughter copies each contain one strand from the parental duplex DNA and one nascent antiparallel strand. This mechanism is conserved from prokaryotes to eukaryotes and

pos: Caulobacter crescentus the chromosome. The CtrA protein, in contrast, acts to block initiation of replication, so it must be removed from the cell before chromosome replication can begin. Multiple additional regulatory pathways integral to cell cycle regulation and involving both phospho signaling pathways and regulated control of protein proteolysis act to assure that DnaA and CtrA are present in the cell just exactly when needed. Each process activated by the proteins of the cell cycle engine involve a cascade of many reactions. The longest subsystem cascade is DNA replication. In "Caulobacter" cells, replication of the chromosome involves about 2 million DNA synthesis

pos: Cell growth briefly at M phase when the nucleus and then the cell divide in two. The process of cell division, called cell cycle, has four major parts called phases. The first part, called G phase is marked by synthesis of various enzymes that are required for DNA replication. The second part of the cell cycle is the S phase, where DNA replication produces two identical sets of chromosomes. The third part is the G phase in which a significant protein synthesis occurs, mainly involving the production of microtubules that are required during the process of division, called mitosis. The fourth phase,

pos: Spindle checkpoint divide, because cell size is big enough or because they receive the appropriate stimulus, they activate the mechanism to enter into the cell cycle, and they duplicate most organelles during S (synthesis) phase, including their centrosome. Therefore, when the cell division process will end, each daughter cell will receive a complete set of organelles. At the same time, during S phase all cells must duplicate their DNA very precisely, a process termed DNA replication. Once DNA replication has finished, in eukaryotes the DNA molecule is compacted and condensed, to form the mitotic chromosomes, each one constituted by two sister chromatids,

pos: Origin recognition complex Cdc6, Tah11 (a.k.a. Cdt1), and the Mcm2-Mcm7 complex. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase. Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase. The ORC is present throughout the cell cycle bound to replication origins, but is only active in late mitosis and early G1. In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR). ORC

pos: Eukaryotic DNA replication continued DNA synthesis and is required for the protection of the genome in the presence of replication stress and potential genotoxic conditions. Thus, ATR-Chk1 activity further prevents potential replication problems at the level of single replication origins by inhibiting initiation of replication throughout the genome, until the signaling cascade maintaining cell-cycle arrest is turned off. Eukaryotic DNA must be tightly compacted in order to fit within the confined space of the nucleus. Chromosomes are packaged by wrapping 147 nucleotides around an octamer of histone proteins, forming a nucleosome. The nucleosome octamer includes two copies of each histone H2A, H2B, H3,

neg: Cell (biology) the S phase of the cell cycle. In meiosis, the DNA is replicated only once, while the cell divides twice. DNA replication only occurs before meiosis I. DNA replication does not occur when the cells divide the second time, in meiosis II. Replication, like all cellular activities, requires specialized proteins for carrying out the job. Between successive cell divisions, cells grow through the functioning of cellular metabolism. Cell metabolism is the process by which individual cells process nutrient molecules. Metabolism has two distinct divisions: catabolism, in which the cell breaks down complex molecules to produce energy and reducing power, and

neg: Cell division cycle 7-related protein kinase the MCM complex at the origin of replication. This is most likely due to the change in conformation allowing the remainder of replication machinery proteins to be loaded. DNA replication can begin after all the necessary proteins are in place. CDC7 has been shown to interact with: Cell division cycle 7-related protein kinase Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the "CDC7" gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this

neg: Cell cycle levels in S and at their lowest near mitosis. Cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication of its DNA (DNA replication) to produce two daughter cells. In bacteria, which lack a cell nucleus, the cell cycle is divided into the B, C, and D periods. The B period extends from the end of cell division to the beginning of DNA replication. DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and

neg: Pre-replication complex to bind the AT-rich portion of the origin of replication in "S. pombe" using AT hook motifs. The mechanism of origin recognition in higher eukaryotes is not well understood but it is thought that the ORC1-6 proteins depend on unusual DNA topology for binding. Assembly of the pre-replication complex only occurs during late M phase and early G1 phase of the cell cycle when cyclin-dependent kinase (CDK) activity is low. This timing and other regulatory mechanisms ensure that DNA replication will only occur once per cell cycle. Assembly of the pre-RC relies on prior origin recognition, either by DnaA in

neg: Pre-replication complex Pre-replication complex A pre-replication complex (pre-RC) is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the same genetic information as the parent cell. Accordingly, formation of the pre-RC is a very important part of the cell cycle. As organisms evolved and became increasingly more complex, so did their pre-RCs. The following is a summary of the components of the pre-RC amongst the different domains of life.

neg: Cell cycle Cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication of its DNA (DNA replication) to produce two daughter cells. In bacteria, which lack a cell nucleus, the cell cycle is divided into the B, C, and D periods. The B period extends from the end of cell division to the beginning of DNA replication. DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and the splitting of the bacterial cell into two daughter

neg: Licensing factor Licensing factor A licensing factor is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. They are thought to primarily occur in eukaryotic cells, since prokaryotes use simpler systems to initiate replication. Origins of replication represent start sites for DNA replication and so their "firing" must be regulated to maintain the correct karyotype of the cell in question. The origins are required to fire only once per cell cycle, an observation that led to the postulated existence of licensing factors by biologists in the first place. If the origins were

neg: Lucy Shapiro cell, has a tail-like flagellum that helps it swim; the other daughter has a stalk which anchors it to a surface. Swarmer cells become stalked cells after a short period of motility. Chromosome replication and cell division only occur in stalked cells. Rather than containing an evenly dispersed mixture of proteins, the single celled "Caulobacter" resembles a highly organized factory, with specific "machinery" regulating each step in the cell cycle to ensure that changes occur at developmentally appropriate times. DNA is copied once per cycle by a particular group of molecules. Once a single DNA copy is placed in each

neg: Cell cycle checkpoint network of regulatory proteins, known as the cell cycle control system, which monitors and dictates the progression of the cell through the cell cycle. This system acts like a timer, or a clock, which sets a fixed amount of time for the cell to spend in each phase of the cell cycle, while at the same time it also responds to information received from the processes it controls. The cell cycle checkpoints play an important role in the control system by sensing defects that occur during essential processes such as DNA replication or chromosome segregation, and inducing a cell cycle

neg: Replication timing with relative ease indicates that we will soon have a wealth of information about where and when large changes in chromosome folding occur during development and in different diseases. Replication timing Replication timing refers to the order in which segments of DNA along the length of a chromosome are duplicated. In eukaryotic cells (cells that package their DNA within a nucleus), chromosomes consist of very long linear double-stranded DNA molecules. During the S-phase of each cell cycle (Figure 1), all of the DNA in a cell is duplicated in order to provide one copy to each of the daughter cells

neg: Eukaryotic DNA replication of their localization to the replication fork. Loading of Mcm proteins can only occur during the G of the cell cycle, and the loaded complex is then activated during S phase by recruitment of the Cdc45 protein and the GINS complex to form the active Cdc45–Mcm–GINS (CMG) helicase at DNA replication forks. Mcm activity is required throughout the S phase for DNA replication. A variety of regulatory factors assemble around the CMG helicase to produce the ‘Replisome Progression Complex’ which associates with DNA polymerases to form the eukaryotic replisome, the structure of which is still quite poorly defined in comparison

neg: Mamavirus Mamavirus possesses its own transcription machinery, and it packages transcription proteins in its particles. Transcription is believed to occur in the core particles. The core releases viral DNA and forms a cytoplasmic replication factory where DNA replication begins and transcription of late genes occurs. The replication factory forms around the viral core and expands until it occupies a large fraction of the amoeba cell volume. Later stages of the replication cycle involve partially assembled procapsids undergoing DNA packaging. While the mimiviridae were a surprise themselves, mamavirus contained an even bigger surprise. While looking at mamavirus under the electron microscope, Raoult

neg: Large tumor antigen after which the helicase continues unwinding. The major functions of LTag in the viral life cycle involve dysregulation of the host cell's cell cycle and replication of the virus's circular DNA genome. Because polyomavirus genome replication relies on the DNA replication machinery of the host cell, the cell must be in S phase (the part of the cell cycle in which the host cell's genome is normally replicated) in order to provide the necessary molecular machinery for viral DNA replication. The SV40 LTag can induce S phase and activate the host cell's DNA damage response. Coordinated actions of the OBD

neg: Bruce William Stillman made up of six subunits that binds to cellular origins of DNA replication and coordinates the entire process of initiating a complete cycle of DNA replication throughout the entire cell genome. Soon after the discovery of ORC, Stillman’s group identified other initiation proteins that together form the pre-replication complex (pre-RC), which makes chromosomes competent for the subsequent initiation of DNA replication during the S phase of the cell cycle. His group’s recent studies have revealed the intricate details of the mechanism of the initiation of DNA replication and illuminated how this process is regulated throughout the cell cycle, including the

neg: Cdc6 hence the pre-RC is activated but not formed. This change assures that DNA replication is performed only once per cell cycle. It has been shown that overexpression of Cdc6p does not induce re-replication in cognate cells, probably due to inhibition through CDK that resets the cell cycle clock to G1. Nevertheless, it has been suggested that regulation of Cdc6p is one of several redundant mechanisms that prevent re-replication of the DNA in eukaryotic cells. The crystallographic structure of a Cdc6p/Orc1-related protein from Pyrobaculum aerophilum (see Pyrobaculum) has been solved and three structural domains have been identified. Domain I and II

neg: DNA re-replication decline of CDK activity at the end of mitosis. Thus, CDKs serve a dual role in the regulation of eukaryotic DNA replication: elevated CDK activity initiates replication at the origins and prevents rereplication by inhibiting origin re-licensing. This ensures that no replication origin fires twice in the same cell cycle. Early experimental evidence on the regulation of DNA replication suggests that replication origins exist in one of two states during the cell cycle: a prereplicative state in G1 and a postreplicative state from the moment of initiation until passage through mitosis. Origins of replication alternate between these two distinct states

neg: Centrosome cycle. During the prophase in the process of cell division called mitosis, the centrosomes migrate to opposite poles of the cell. The mitotic spindle then forms between the two centrosomes. Upon division, each daughter cell receives one centrosome. Aberrant numbers of centrosomes in a cell have been associated with cancer. Doubling of a centrosome is similar to DNA replication in two respects: the semiconservative nature of the process and the action of CDK2 as a regulator of the process. But the processes are essentially different in that centrosome doubling does not occur by template reading and assembly. The mother centriole

neg: Eukaryotic DNA replication divided into the daughter cells at mitosis. The major enzymatic functions carried out at the replication fork are well conserved from prokaryotes to eukaryotes, but the replication machinery in eukaryotic DNA replication is a much larger complex, coordinating many proteins at the site of replication, forming the replisome. The replisome is responsible for copying the entirety of genomic DNA in each proliferative cell. This process allows for the high-fidelity passage of hereditary/genetic information from parental cell to daughter cell and is thus essential to all organisms. Much of the cell cycle is built around ensuring that DNA replication occurs without

neg: DNA damage (naturally occurring) to progress to mitosis. The three main checkpoints are at G1/s, G2/m, and at the spindle assembly checkpoint regulating progression through anaphase. G1 and G2 checkpoints involve scanning for damaged DNA. During S phase the cell is more vulnerable to DNA damage than any other part of the cell cycle. G2 checkpoint checks for damaged DNA and DNA replication completeness. DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a base missing from the backbone of DNA, or a chemically changed base as 8-OHdG. DNA damage can occur naturally

neg: DNA re-replication DNA re-replication DNA re-replication (or simply rereplication) is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers. To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being partially or fully rereplicated in a given cell cycle. These control mechanisms rely on cyclin-dependent kinase (CDK) activity. DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell

neg: Homology directed repair region to be repaired. In a diploid cell in G1 phase of the cell cycle, such a molecule is present in the form of the homologous chromosome. However, in the G2 stage of the cell cycle (following DNA replication), a second homologous DNA molecule is also present: the sister chromatid. Evidence indicates that, due to the special nearby relationship they share, sister chromatids are not only preferred over distant homologous chromatids as substrates for recombinational repair, but have the capacity to repair more DNA damage than do homologs. During meiosis up to one-third of all homology directed repair events occur

neg: Polyomaviridae small tumor antigen (ST) and large tumor antigen (LT) - are expressed first, from a single alternatively spliced messenger RNA strand. These proteins serve to manipulate the host's cell cycle - dysregulating the transition from G1 phase to S phase, when the host cell's genome is replicated - because host cell DNA replication machinery is needed for viral genome replication. The precise mechanism of this dysregulation depends on the virus; for example, SV40 LT can directly bind host cell p53, but murine polyomavirus LT does not. LT induces DNA replication from the viral genome's non-coding control region (NCCR), after which

neg: Biochemical switches in the cell cycle that parameterization is very important for circuit function. If the dynamics of the input are comparable or faster than the response of the system, the response may appear hysteretic. Three cell cycle switches are described below that achieve abrupt and/or irreversible transitions by exploiting some of the mechanisms described above. The G1/S transition, more commonly known as the Start checkpoint in budding yeast (the restriction point in other organisms) regulates cell cycle commitment. At this checkpoint, cells either arrest before DNA replication (due to limiting nutrients or a pheromone signal), prolong G1 (size control), or begin replication and progress through

neg: Eukaryotic DNA replication recruitment of DNA polymerases. Instead, the pre-RC that is formed during the G of the cell cycle is only activated to unwind the DNA and initiate replication after the cells pass from the G to the S phase of the cell cycle. Once the initiation complex is formed and the cells pass into the S phase, the complex then becomes a replisome. The eukaryotic replisome complex is responsible for coordinating DNA replication. Replication on the leading and lagging strands is performed by DNA polymerase ε and DNA polymerase δ. Many replisome factors including Claspin, And1, replication factor C clamp loader

neg: Eukaryotic DNA replication for docking with Chk1, revealing a specific function of Claspin during DNA replication: the promotion of checkpoint signaling at the replisome. Chk1 signaling is vital for arresting the cell cycle and preventing cells from entering mitosis with incomplete DNA replication or DNA damage. The Chk1-dependent Cdk inhibition is important for the function of the ATR-Chk1 checkpoint and to arrest the cell cycle and allow sufficient time for completion of DNA repair mechanisms, which in turn prevents the inheritance of damaged DNA. In addition, Chk1-dependent Cdk inhibition plays a critical role in inhibiting origin firing during S phase. This mechanism prevents

neg: DNA replication factor CDT1 DNA replication factor CDT1 CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the "CDT1" gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle. The protein encoded by this gene is a key licensing factor in the assembly of pre-replication complexes (pre-RC), which occurs during the G1 phase of the cell cycle. In the assembly of pre-RCs, origin recognition complexes (ORC1-6) recognize and bind to DNA replication origins. CDT1, along with the protein CDC6, are then recruited to the forming pre-RC, followed

neg: Replication timing Replication timing Replication timing refers to the order in which segments of DNA along the length of a chromosome are duplicated. In eukaryotic cells (cells that package their DNA within a nucleus), chromosomes consist of very long linear double-stranded DNA molecules. During the S-phase of each cell cycle (Figure 1), all of the DNA in a cell is duplicated in order to provide one copy to each of the daughter cells after the next cell division. The process of duplicating DNA is called DNA replication, and it takes place by first unwinding the duplex DNA molecule, starting at many locations

neg: Eukaryotic DNA replication Eukaryotic DNA replication Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome. DNA replication is the action of DNA polymerases synthesizing a DNA strand complementary to the original template strand. To synthesize DNA, the double-stranded DNA is unwound by DNA helicases ahead of polymerases, forming a replication fork containing two single-stranded templates. Replication processes permit the copying of a single DNA double helix into two DNA helices, which are

neg: Chromothripsis which contain whole chromosomes or fragments of chromosomes. The segregation of single chromosomes into individual micronuclei explains why DNA fragmentation is isolated to single chromosomes in chromothripsis. These micronuclei undergo defective DNA replication, which is slower than DNA replication in the main nucleus and causes a proximal DNA damage response (DDR) to be initiated. However, DNA repair and cell cycle checkpoint activation fail to follow. Consequently, chromosomes that are not correctly replicated in micronuclei become fragmented. The method by which the pulverization of these chromosomes occur is not fully understood, but it is thought to be caused either by aberrant

neg: Control of chromosome duplication subunits reduces the amount of BrdU (a marker of active replication), incorporated. Studies in "Xenopus" extracts show that immuno-depletion of ORC subunits inhibits DNA replication of "Xenopus" sperm nuclei. In some organisms, the ORC appears to associate with chromatin throughout the cell cycle, but in others it dissociates at specific stages of the cell cycle. Cdc6 and Cdt1 assemble on the ORC and recruit the Mcm proteins. Homologs for these two S. cerevisiae proteins have been found in all eukaryotes. Studies have shown that these proteins are necessary for DNA replication. Mutations in "S. pombe" cdt1 blocked DNA replication. Mcm

neg: Eukaryotic DNA replication loaded onto the chromatin, as a component of the pre-RC at the origin of replication during the G stage of the cell cycle. Cell division cycle 45 (Cdc45) protein is a critical component for the conversion of the pre-replicative complex to the initiation complex. The Cdc45 protein assembles at replication origins before initiation and is required for replication to begin in "Saccharomyces cerevisiae", and has an essential role during elongation. Thus, Cdc45 has central roles in both initiation and elongation phases of chromosomal DNA replication. Cdc45 associates with chromatin after the beginning of initiation in late G stage and during

neg: Cell division cycle 7-related protein kinase Cell division cycle 7-related protein kinase Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the "CDC7" gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein. The product encoded by this gene is predominantly localized in the nucleus and is a cell division cycle protein with kinase activity. The protein is a serine-threonine kinase that is activated by another protein called either Dbf4

neg: G2-M DNA damage checkpoint G2-M DNA damage checkpoint The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms ranging from yeast to mammals, ensuring that cells don't initiate mitosis until damaged DNA or incompletely replicated DNA is sufficiently repaired after replication. Cells that have a defective G2-M checkpoint enter mitosis before repairing their DNA, leading to apoptosis or death after cell division. The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at different checkpoints of the cell cycle. Different phases of the cell cycle experience activation and/or deactivation of specific cyclin-CDK complexes.

neg: DNA damage (naturally occurring) adult mammals, and can cause aging. (Also see DNA damage theory of aging.) In replicating cells, such as cells lining the colon, errors occur upon replication pass damages in the template strand of DNA or during repair of DNA damages. These errors can give rise to mutations or epigenetic alterations. Both of these types of alteration can be replicated and passed on to subsequent cell generations. These alterations can change gene function or regulation of gene expression and possibly contribute to progression to cancer. Throughout the cell cycle there are various checkpoints to ensure the cell is in good condition

neg: Eukaryotic DNA replication first appears in S-phase and is degraded at the metaphase-anaphase transition, possibly through ubiquination by anaphase promoting complex (APC). Various cell cycle checkpoints are present throughout the course of the cell cycle that determine whether a cell will progress through division entirely. Importantly in replication the G, or restriction, checkpoint makes the determination of whether or not initiation of replication will begin or whether the cell will be placed in a resting stage known as G. Cells in the G stage of the cell cycle are prevented from initiating a round of replication because the minichromosome maintenance proteins are not

neg: Eukaryotic DNA replication completes copying the region. There are programmed replication fork barriers (RFBs) bound by RFB proteins in various locations, throughout the genome, which are able to terminate or pause replication forks, stopping progression of the replisome. DNA replication is a tightly orchestrated process that is controlled within the context of the cell cycle. Progress through the cell cycle and in turn DNA replication is tightly regulated by the formation and activation of pre-replicative complexs (pre-RCs) which is achieved through the activation and inactivation of cyclin-dependent kinases (Cdks, CDKs). Specifically it is the interactions of cyclins and cyclin dependent kinases that are

neg: Eukaryotic DNA replication responsible for the transition from G into S-phase. During the G phase of the cell cycle there are low levels of CDK activity. This low level of CDK activity allows for the formation of new pre-RC complexes but is not sufficient for DNA replication to be initiated by the newly formed pre-RCs. During the remaining phases of the cell cycle there are elevated levels of CDK activity. This high level of CDK activity is responsible for initiating DNA replication as well as inhibiting new pre-RC complex formation. Once DNA replication has been initiated the pre-RC complex is broken down. Due

neg: Cell cycle maternally loaded mRNA. Analyses of synchronized cultures of "Saccharomyces cerevisiae" under conditions that prevent DNA replication initiation without delaying cell cycle progression showed that origin licensing decreases the expression of genes with origins near their 3' ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation. Cell cycle checkpoints are used by the cell to monitor and

neg: Azacitidine through the carbon-5 atom, but this latter reaction does not occur with azacytosine because its carbon-5 is substituted by nitrogen, leaving the enzyme covalently bound to DNA and blocking its DNA methyltransferase function. In addition, the covalent protein adduction also compromises the functionality of DNA and triggers DNA damage signaling, resulting in the degradation of trapped DNA methyltransferases. As a consequence, methylation marks become lost during DNA replication. Azacitidine causes anemia (low red blood cell counts), neutropenia (low white blood cell counts), and thrombocytopenia (low platelet counts), and patients should have frequent monitoring of their complete blood counts, at least

neg: DNA repair the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the G1/S and G2/M boundaries. An intra-S checkpoint also exists. Checkpoint activation is controlled by two master kinases, ATM and ATR. ATM responds to DNA double-strand breaks and disruptions in chromatin structure, whereas ATR primarily responds to stalled replication forks. These kinases phosphorylate downstream targets in a signal transduction cascade, eventually leading to cell cycle arrest. A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified. These proteins seem to be required for transmitting the checkpoint activation signal to

neg: Eukaryotic DNA replication M phase. A complete and intact six subunit Mcm complex is required to enter into the cell nucleus. In "S. cerevisiae", nuclear export is promoted by cyclin-dependent kinase (CDK) activity. Mcm proteins that are associated with chromatin are protected from CDK export machinery due to the lack of accessibility to CDK. During the G stage of the cell cycle, the replication initiation factors, origin recognition complex (ORC), Cdc6, Cdt1, and minichromosome maintenance (Mcm) protein complex, bind sequentially to DNA to form the pre-replication complex (pre-RC). At the transition of the G stage to the S phase of the cell cycle,

neg: Eukaryotic DNA replication to the fact that CDK levels remain high during the S phase, G, and M phases of the cell cycle no new pre-RC complexes can be formed. This all helps to ensure that no initiation can occur until the cell division is complete. In addition to cyclin dependent kinases a new round of replication is thought to be prevented through the downregulation of Cdt1. This is achieved via degradation of Cdt1 as well as through the inhibitory actions of a protein known as geminin. Geminin binds tightly to Cdt1 and is thought to be the major inhibitor of re-replication. Geminin

neg: Eukaryotic DNA replication a series of steps of protein assemblies at origins of replication, mainly focusing the regulation of DNA replication on the association of the MCM helicase with the DNA. These origins of replication direct the number of protein complexes that will form to initiate replication. In prokaryotic DNA replication regulation focuses on the binding of the DnaA initiator protein to the DNA, with initiation of replication occurring multiple times during one cell cycle. Both prokaryotic and eukaryotic DNA use ATP binding and hydrolysis to direct helicase loading and in both cases the helicase is loaded in the inactive form. However, eukaryotic

neg: Cell division cycle 7-related protein kinase in the yeast "Saccharomyces cerevisiae" or ASK in mammals. The Cdc7/Dbf4 complex adds a phosphate group to the minichromosome maintenance (MCM) protein complex allowing for the initiation of DNA replication in mitosis (as explained in the Cdc7 and Replication section below). Although expression levels of the protein appear to be constant throughout the cell cycle, the protein kinase activity appears to increase during S phase. It has been suggested that the protein is essential for initiation of DNA replication and that it plays a role in regulating cell cycle progression. Overexpression of this gene product may be associated with neoplastic

neg: Control of chromosome duplication Control of chromosome duplication In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle. A key feature of the DNA replication mechanism in eukaryotes is that it is designed to replicate relatively large genomes rapidly and with high fidelity. Replication is initiated at multiple origins of replication on multiple chromosomes simultaneously so that the duration of S phase is not limited by the total amount of DNA. This flexibility in genome size comes at a cost: there has to be a high-fidelity control system that coordinates multiple replication origins so that

neg: DNA repair reversion of previously-inhibited defects. It has become apparent over the past several years that the DNA damage response acts as a barrier to the malignant transformation of preneoplastic cells. Previous studies have shown an elevated DNA damage response in cell-culture models with oncogene activation and preneoplastic colon adenomas. DNA damage response mechanisms trigger cell-cycle arrest, and attempt to repair DNA lesions or promote cell death/senescence if repair is not possible. Replication stress is observed in preneoplastic cells due to increased proliferation signals from oncogenic mutations. Replication stress is characterized by: increased replication initiation/origin firing; increased transcription and collisions of transcription-replication

neg: Small tumor antigen and LTag interact through their J domains with Hsc70 to increase its ATPase activity. Because polyomavirus genome replication relies on the DNA replication machinery of the host cell, the cell must be in S phase (the part of the cell cycle in which the host cell's genome is normally replicated) in order to provide the necessary molecular machinery for viral DNA replication. Viral proteins therefore promote dysregulation of the cell cycle and entry into S phase. This function is usually primarily provided by LTag through its interactions with retinoblastoma protein and p53. STag contributes to this process through its interaction

neg: Molecular evolution drift or natural selection. Mutations are permanent, transmissible changes to the genetic material (DNA or RNA) of a cell or virus. Mutations result from errors in DNA replication during cell division and by exposure to radiation, chemicals, and other environmental stressors, or viruses and transposable elements. Most mutations that occur are single nucleotide polymorphisms which modify single bases of the DNA sequence, resulting in point mutations. Other types of mutations modify larger segments of DNA and can cause duplications, insertions, deletions, inversions, and translocations. Most organisms display a strong bias in the types of mutations that occur with strong influence

neg: Eukaryotic DNA replication (ORC) with a replication origin is required to recruit both cell division cycle 6 protein (Cdc6) and chromatin licensing and DNA replication factor 1 protein (Cdt1), which initiate the assembly of the pre-RC. Both Cdc6 and Cdt1 proteins associate with the already bound ORC independently from each other. The ORC, Cdc6, and Cdt1 together are required for the stable association of the minichromosome maintenance (Mcm 2-7) complex proteins with replicative origins during G phase of the cell cycle. Eukaryotic origins of replication control the formation of a number of protein complexes that lead to the assembly of two bidirectional DNA

neg: Eukaryotic DNA replication expressed. Transition into the S-phase indicates replication has begun. In order to preserve genetic information during cell division, DNA replication must be completed with high fidelity. In order to achieve this task, eukaryotic cells have proteins in place during certain points in the replication process that are able to detect any errors during DNA replication and are able to preserve genomic integrity. These checkpoint proteins are able to stop the cell cycle from entering mitosis in order to allow time for DNA repair. Checkpoint proteins are also involved in some DNA repair pathways, while they stabilize the structure of the

neg: Pre-replication complex MCM10. MCM10 cooperates with MCM2-7 in the recruitment of Cdc45. Cdc45 then recruits key components of the replisome; the replicative DNA polymerase α and its primase. DNA replication can then begin. During each cell cycle, it is important that the genome be completely replicated once and only once. Formation of the pre-replication complex during late M and early G1 phase is required for genome replication, but after the genome has been replicated the pre-RC must not form again until the next cell cycle. In S. cerevisiae, CDKs prevent formation of the replication complex during late G1, S, and G2 phases

neg: Control of chromosome duplication to chromatin in a Cdc7/Dbf4 dependant manner. Control of chromosome duplication In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle. A key feature of the DNA replication mechanism in eukaryotes is that it is designed to replicate relatively large genomes rapidly and with high fidelity. Replication is initiated at multiple origins of replication on multiple chromosomes simultaneously so that the duration of S phase is not limited by the total amount of DNA. This flexibility in genome size comes at a cost: there has to be a high-fidelity control system

neg: DNA replication factor CDT1 by minichromosome maintenance complexes (MCM2-7). The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin, which inhibits its, and by SCF, which ubiquinates the protein to tag it for proteasomal degradation. This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cycle. CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthologs in other species include: DNA replication factor CDT1 has been shown to interact with SKP2. Cdt1 is recruited by the origin recognition complex in origin licensing.

neg: Eukaryotic DNA replication S phase–specific cyclin-dependent protein kinase (CDK) and Cdc7/Dbf4 kinase (DDK) transform the pre-RC into an active replication fork. During this transformation, the pre-RC is disassembled with the loss of Cdc6, creating the initiation complex. In addition to the binding of the Mcm proteins, cell division cycle 45 (Cdc45) protein is also essential for initiating DNA replication. Studies have shown that Mcm is critical for the loading of Cdc45 onto chromatin and this complex containing both Mcm and Cdc45 is formed at the onset of the S phase of the cell cycle. Cdc45 targets the Mcm protein complex, which has been

neg: Minichromosome maintenance MCM2-7 to unwind DNA. Following DNA polymerase loading, bidirectional DNA replication commences. During S phase, Cdc6 and Cdt1 are degraded or inactivated to block additional pre-RC formation, and bidirectional DNA replication ensues. When the replication fork encounters lesions in the DNA, the S-phase checkpoint response slows or stops fork progression and stabilizes the association of MCM2-7 with the replication fork during DNA repair. The replication licensing system acts to ensure that the no section of the genome is replicated more than once in a single cell cycle. The inactivation of any of at least five of the six MCM subunits

neg: Replication stress Uncoordinated replication–transcription conflicts and unscheduled R-loop accumulation are significant contributors. The events that lead to genome instability occur in the cell cycle prior to mitosis, specifically in the S phase. Disturbance to this phase can generate negative effects, such as inaccurate chromosomal segregation, for the upcoming mitotic phase. The two processes that are responsible for damage to the S phase are oncogenic activation and tumor suppressor inactivation. They have both been shown to speed up the transition from the G1 phase to the S phase, leading to inadequate amounts of DNA replicative components. These losses can contribute to the DNA

neg: Pre-replication complex to cause Meier-Gorlin syndrome, which is characterized by absent or hypoplastic patellae, small ears, impaired pre- and post-natal growth, and microcephaly. Known mutations are in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes. The disease phenotype probably originates from reduced ability of cells to proliferate, reduced cell number, and general growth failure. Pre-replication complex A pre-replication complex (pre-RC) is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will

neg: Cell cycle checkpoint Cell cycle checkpoint All living organisms are the products of repeated rounds of cell growth and division. During this process, known as the cell cycle, a cell duplicates its contents and then divides in two. The purpose of the cell cycle is to accurately duplicate each organism's DNA and then divide the cell and its contents evenly between the two resulting cells. In eukaryotes, the cell cycle consists of four main stages: G, during which a cell is metabolically active and continuously grows; S phase, during which DNA replication takes place; G, during which cell growth continues and the cell

neg: Neuronal cell cycle and Greene, L. a. (1998). Cyclin-dependent kinases participate in death of neurons evoked by DNA- damaging agents. J. Cell Biol. 143, 457–467. Smith, D.S., Leone, G., DeGregori, J., Ahmed, M.N., Qumsiyeh, M.B., and Nevins, J.R. (2000). Induction of DNA replication in adult rat neurons by deregulation of the retinoblastoma/E2F G1 cell cycle pathway. Cell Growth Differ. 11, 625–633. Williams, G.H., and Stoeber, K. (2012). The cell cycle and cancer. 352–364. Yang, Y., Mufson, E.J., and Herrup, K. (2003). Neuronal Cell Death Is Preceded by Cell Cycle Events at All Stages of Alzheimer’s Disease. J. Neurosci. 23, 2557–2563. Yasutis, K.M., and

neg: Cell cycle and of enzymes required for DNA replication. The G cyclin-CDK complexes also promote the degradation of molecules that function as S phase inhibitors by targeting them for ubiquitination. Once a protein has been ubiquitinated, it is targeted for proteolytic degradation by the proteasome. However, results from a recent study of E2F transcriptional dynamics at the single-cell level argue that the role of G1 cyclin-CDK activities, in particular cyclin D-CDK4/6, is to tune the timing rather than the commitment of cell cycle entry. Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes assembled during G phase on DNA

neg: G1 phase not move into the S phase include insufficient cell growth, damaged DNA, or other preparations have not been completed. At the G/S checkpoint, formation of the G/S cyclin with Cdk to form a complex commits the cell to a new division cycle. These complexes then activate S-Cdk complexes that move forward with DNA replication in the S phase. Concurrently, anaphase-promoting complex (APC) activity decreases significantly, allowing S and M cyclins to become activated. If a cell does not clear to pass through to the S phase, it enters the dormant G phase in which there is no cellular growth or

neg: Okazaki fragments cells can take up to 400 hours. Eukaryotes also have a distinct operation for replicating the telomeres at the end of their last chromosomes. Prokaryotes have circular chromosomes, causing no ends to synthesize. Prokaryotes have a short replication process that occurs continuously; eukaryotic cells, on the other hand, only undertake DNA replication during the S-phase of the cell cycle. The similarities are the steps for the DNA replication. In both prokaryotes and eukaryotes, replication is accomplished by unwinding the DNA by an enzyme called the DNA helicase. New strands are created by enzymes called DNA polymerases. Both of these follow

neg: Origin recognition complex Origin recognition complex In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes. ORC is a central component for eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle. ORC directs DNA replication throughout the genome and is required for its initiation. ORC bound at replication origins serves as the foundation for assembly of the pre-replication complex (pre-RC), which includes

neg: DNA repair regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. Unlike proteins and RNA, DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. DNA damage can be subdivided into two main types: The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these wrong bases carry

neg: David M. Gilbert David M. Gilbert David M. Gilbert is an American molecular biologist, known for work in DNA replication. Gilbert is J. Herbert Taylor Distinguished Professor of Molecular Biology in the Department of Biological Science and Co-founder and Associate Director of the Center for Genomics and Personalized Medicine at Florida State University. Gilbert’s work focuses on the mechanisms regulating DNA replication during the cell cycle and the relationship between DNA replication and structural and functional organization of chromosomes, most recently during differentiation in human and mouse embryonic stem cells and in pediatric leukemia. Gilbert received his BA degrees in Biochemistry/Cell Biology and

neg: DNA methylation Bacterial viability is compromised in dam mutants that also lack certain other DNA repair enzymes, providing further evidence for the role of Dam in DNA repair. One region of the DNA that keeps its hemimethylated status for longer is the origin of replication, which has an abundance of GATC sites. This is central to the bacterial mechanism for timing DNA replication. SeqA binds to the origin of replication, sequestering it and thus preventing methylation. Because hemimethylated origins of replication are inactive, this mechanism limits DNA replication to once per cell cycle. Expression of certain genes, for example those coding for

neg: MCM5 interact with: MCM5 DNA replication licensing factor MCM5 is a protein that in humans is encoded by the "MCM5" gene. The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation. MCM5 has been

neg: MCM5 MCM5 DNA replication licensing factor MCM5 is a protein that in humans is encoded by the "MCM5" gene. The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation. MCM5 has been shown to

neg: Lysogenic cycle the lytic cycle. Lysogenic cycles can also occur in eukaryotes, although the method of DNA incorporation is not fully understood. The difference between lysogenic and lytic cycles is that, in lysogenic cycles, the spread of the viral DNA occurs through the usual prokaryotic reproduction, whereas a lytic cycle is more immediate in that it results in many copies of the virus being created very quickly and the cell is destroyed. One key difference between the lytic cycle and the lysogenic cycle is that the lysogenic cycle does not lyse the host cell straight away. Phages that replicate only via the

neg: Licensing factor not carefully regulated then DNA replication could be restarted at that origin giving rise to multiple copies of a section of DNA. This could be damaging to cells and could have detrimental effects on the organism as a whole. The control that licensing factors exert over the cycle represents a flexible system, necessary so that different cell types in an organism can control the timing of DNA replication to their own cell cycles. The factors themselves are found in different places in different organisms. For example in metazoan organisms, they are commonly synthesised in the cytoplasm of the cell to

neg: DNA replication site-binding protein, or Ter protein. Because bacteria have circular chromosomes, termination of replication occurs when the two replication forks meet each other on the opposite end of the parental chromosome. "E. coli" regulates this process through the use of termination sequences that, when bound by the Tus protein, enable only one direction of replication fork to pass through. As a result, the replication forks are constrained to always meet within the termination region of the chromosome. Within eukaryotes, DNA replication is controlled within the context of the cell cycle. As the cell grows and divides, it progresses through stages in

neg: Eukaryotic DNA replication the S phase of the cell cycle. Cdc45 physically associates with Mcm5 and displays genetic interactions with five of the six members of the Mcm gene family and the ORC2 gene. The loading of Cdc45 onto chromatin is critical for loading other various replication proteins, including DNA polymerase α, DNA polymerase ε, replication protein A (RPA) and proliferating cell nuclear antigen (PCNA) onto chromatin. Within a "Xenopus" nucleus-free system, it has been demonstrated that Cdc45 is required for the unwinding of plasmid DNA. The "Xenopus" nucleus-free system also demonstrates that DNA unwinding and tight RPA binding to chromatin occurs only

neg: Cell division control protein 4 of Sic1. Each bond to a Sic1-Phosphate is weak, but together the binding is strong enough to enable Sic1-degradation via the pathway described before. Hence, in this case ultrasensitivity allows precise definition ("fine tuning") of the time point in which destruction of Sic1 occurs, leading to initiation of the next step in the cell cycle (-> DNA replication). Up until now it is not satisfyingly understood how Cdc4 triggers G2-M transition. In general, the second degradation complex involved in cell cycle progression, APC, is responsible for proteolysis at that stage. However, experimental data suggests that Cdc4 function in G2/M transition

neg: Reverse transcriptase family, which is vital to their replication. There are three different replication systems during the life cycle of a retrovirus. First of all, the reverse transcriptase synthesizes viral DNA from viral RNA, and then from newly made complementary DNA strand. The second replication process occurs when host cellular DNA polymerase replicates the integrated viral DNA. Lastly, RNA polymerase II transcribes the proviral DNA into RNA, which will be packed into virions. Therefore, mutation can occur during one or all of these replication steps. Reverse transcriptase has a high error rate when transcribing RNA into DNA since, unlike most other DNA

neg: Cell damage damage (see DNA damage (naturally occurring) and Sedelnikova et al.). In humans, about 10,000 oxidative DNA damages occur per cell per day. In the rat, which has a higher metabolic rate than humans, about 100,000 oxidative DNA damages occur per cell per day. In aerobically growing bacteria, ROS appear to be a major source of DNA damage, as indicated by the observation that 89% of spontaneously occurring base substitution mutations are caused by introduction of ROS-induced single-strand damages followed by error-prone replication past these damages. Oxidative DNA damages usually involve only one of the DNA strands at any damaged site,

neg: Cell division cycle 7-related protein kinase done at this point to try to fix the CDC7 gene so replication can occur. By copying and replacing the altered area with a very similar area on the sister homolog chromosome, the gene can be replicated as if nothing was ever wrong on the chromosome. However, when the cell enters this arrested state, levels of p53 may increase. These increased levels of p53 may initiate cell death. After chromatin undergoes changes in telophase of mitosis, the hexameric protein complex of MCM proteins 2-7 forms part of the pre-replication complex (pre-RC) by binding to the chromatin and other aiding proteins

neg: Okazaki fragments prokaryotic E. coli chromosome has only a single origin of replication. Replication in prokaryotes occurs inside of the cytoplasm, and this all begins the replication that is formed of about 100 to 200 or more nucleotides. Eukaryotic DNA molecules have a significantly larger number of replicons, about 50,000 or more; however, replication does not occur at the same time on all of the replicons. In eukaryotes, DNA replication takes place in the nucleus. A plethora replication form in just one replicating DNA molecule, the start of DNA replication is moved away by the multi-subunit protein. This replication is slow, and

neg: SeqA protein domain SeqA protein domain In molecular biology the protein domain SeqA is one found in bacteria and archaea. The function of this protein domain is highly important in DNA replication. The protein negatively regulates the initiation of DNA replication at the origin of replication, in "Escherichia coli", OriC. Additionally the protein plays a further role in sequestration. The importance of this protein is vital, without its help in DNA replication, cell division and other crucial processes could not occur. This protein domain is thought to be part of a much larger protein complex which includes other proteins such as SeqB. DNA

neg: RAD17 RAD17 Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the "RAD17" gene. The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by ATR after the damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after

neg: Histone This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA separating each pair of nucleosomes (also referred to as linker DNA). Higher-order structures include the 30 nm fiber (forming an irregular zigzag) and 100 nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins. Histones are subdivided into canonical replication-dependent histones that are expressed during the S-phase of cell cycle and replication-independent histone variants, expressed during the whole cell cycle. In animals, genes encoding canonical histones are typically

neg: DNA replication factor CDT1 Null-mutations for CDT1 are lethal in yeast; the spores undergo mitosis without DNA replication. The overexpression of CDT1 causes rereplication in H. sapiens, which activates the CHK1 pathway, preventing entry into mitosis. DNA replication factor CDT1 CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the "CDT1" gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle. The protein encoded by this gene is a key licensing factor in the assembly of pre-replication complexes (pre-RC), which occurs during the G1 phase of the

neg: Geminin of geminin by RNAi leads to impairment of DNA replication during the following cell cycle in many cancer cell lines, no such cell cycle defect is seen in primary and immortalized cell lines (although Cdt1 levels are still reduced in these cells). Geminin therefore is an important player in ensuring that one and only one round of replication occurs during each cell cycle. Geminin promotes early neural fate commitment by hyperacetylating the chromatin. This effect allows neural genes to be accessible for transcription, promoting the expression of these genes. Ultimately, geminin allows cells uncommitted to any particular lineage to acquire

neg: Homologous recombination future generations in equal proportion. This represents linkage between the two genes greater than would be expected from genes that independently assort during meiosis. Double-strand breaks can be repaired through homologous recombination or through non-homologous end joining (NHEJ). NHEJ is a DNA repair mechanism which, unlike homologous recombination, does not require a long homologous sequence to guide repair. Whether homologous recombination or NHEJ is used to repair double-strand breaks is largely determined by the phase of cell cycle. Homologous recombination repairs DNA before the cell enters mitosis (M phase). It occurs during and shortly after DNA replication, in the S

neg: DNA re-replication during the cell cycle. A licensing factor which is required for replication initiation binds to origins in the prereplicative state. At the G1/S transition, the factor is inactivated and cannot be restored until the cell cycle has concluded. The identification and characterization of the ORC, Cdc6, Cdt1, and the MCM complex proteins as the licensing factor gives credence to this model and suggests a means by which the oscillatory nature of CDKs in the cell cycle can regulate rereplication. Rereplication regulation is best understood in budding yeast. "Saccharomyces cerevisiae" cells prevent rereplication by directly regulating pre-RC assembly through the CDK-mediated

neg: Cell cycle analysis G are the cells just prior entering S, with their growth (RNA and protein content, size) similar to that of the cells initiating DNA replication. Similar cell cycle compartments are also recognized by multiparameter analysis that includes measurement of expression of cyclin D1, cyclin E, cyclin A and cyclin B1, each in relation to DNA content Concurrent measurement of DNA content and of incorporation of DNA precursor 5-bromo-2'-deoxyuridine (BrdU) by flow cytometry is an especially useful assay, that has been widely used in analysis of the cell cycle in vitro and in vivo. However, the incorporation of 5-ethynyl-2'-deoxyuridine (EdU), the

neg: DNA adduct a piece of DNA that has DMBA attached to it. The presence of such an adduct indicates prior exposure to a potential carcinogen, but does not by itself indicate the presence of cancer in the subject animal. Chemicals that form DNA adducts include: DNA adducts include: By-products include: When a chemical binds to DNA, the DNA becomes damaged, and proper and complete replication cannot occur to make the normal intended cell. This could be the start of a mutation, or mutagenesis. Without effective DNA repair, which happens naturally under normal circumstances, this can lead to carcinogenesis, the beginnings of cancer.

neg: Eukaryotic DNA replication formation of single-stranded DNA occurs frequently, more often during replication stress. ATR-ATRIP is able to arrest the cell cycle to preserve genome integrity. ATR is found on chromatin during S phase, similar to RPA and claspin. The generation of single-stranded DNA tracts is important in initiating the checkpoint pathways downstream of replication damage. Once single-stranded DNA becomes sufficiently long, single-stranded DNA coated with RPA are able to recruit ATR-ATRIP. In order to become fully active, the ATR kinase rely on sensor proteins that sense whether the checkpoint proteins are localized to a valid site of DNA replication stress. The RAD9-HUS1-Rad1

neg: Cell division in the first division, and sister chromatids are separated in the second division. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor. Prokaryotes (bacteria) undergo a vegetative cell division known as binary fission, where their genetic material is segregated equally into two daughter cells. All cell divisions, regardless of organism, are preceded by a single round of DNA replication. For simple unicellular microorganisms such as the amoeba, one cell division is equivalent to reproduction – an

neg: ATM serine/threonine kinase ATM serine/threonine kinase ATM serine/threonine kinase, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2, BRCA1, NBS1 and H2AX are tumor suppressors. The protein was named for the disorder ataxia telangiectasia caused by mutations of ATM. Throughout the cell cycle DNA is monitored for damage. Damages result from errors during replication, by-products of metabolism, general toxic drugs or ionizing radiation. The cell cycle has

neg: Geminiviridae enzymes necessary for DNA replication, making it difficult for the virus to replicate. To overcome this block geminiviruses can induce plant cells to reenter the cell cycle from a quiescent state so that viral replication can occur. These viruses may have evolved from a phytoplasma plasmid. Geminiviruses are capable of horizontal gene transfer of genetic information to the plant host. Geminiviridae Geminiviridae is a family of plant viruses. There are currently over 360 species in this family, divided among 9 genera. Diseases associated with this family include: bright yellow mosaic, yellow mosaic, yellow mottle, leaf curling, stunting, streaks, reduced yields.

neg: DNA replication access on an opposite direction of the stalled fork and duplicate the un-replicated sites. As other mechanism of the rescue there is application of dormant replication origins that excess origins don't fire in normal DNA replication. Most bacteria do not go through a well-defined cell cycle but instead continuously copy their DNA; during rapid growth, this can result in the concurrent occurrence of multiple rounds of replication. In "E. coli", the best-characterized bacteria, DNA replication is regulated through several mechanisms, including: the hemimethylation and sequestering of the origin sequence, the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and