Dna replication and sister chromatid cohesion. Medical search. Frequent questions

In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. (wikipedia.org)
Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles. (wikipedia.org)
At entry to mitosis, Sororin is phosphorylated and replaced again by Wapl, leading to loss of cohesion. (wikipedia.org)
It is well known that the products of chromosome replication are paired to ensure that the sisters segregate away from each other during mitosis. (rupress.org)
Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)
Uneven distribution of sister chromatids in mitosis or failure to repair DNA breaks results in aneuploidy or chromosome translocations, which are two prevalent forms of genomic instability in cancer cells. (packard.org)
We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. (silverchair.com)
smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. (silverchair.com)
During mitosis, cohesion between sisters is maintained as chromosomes condense, attach to the mitotic spindle in a bipolar orientation, and congress to the metaphase plate. (silverchair.com)
Following replication, cohesin embraces both sister chromatids and holds them together until mitosis. (advancedsciencenews.com)
Subsequently, during mitosis, the cohesin ring is opened, releasing the sister chromatids and enabling their segregation to daughter cells (see Figure 2). (advancedsciencenews.com)
2) the two sister DNA molecules remain tightly associated with each other from the moment of DNA replication until the metaphase-anaphase transition of the subsequent mitosis. (europa.eu)
I will develop experimental conditions to mimic different degrees of "cohesion fatigue" (partial loss of sister chromatid cohesion), as well as a variety of abnormalities in chromosome structure and size and quantitatively evaluate how chromosome cohesion and condensation influence chromosome dynamics and signaling of the surveillance mechanism that control mitosis (the Spindle Assembly Checkpoint). (europa.eu)

Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. (wikipedia.org)
Establishment of cohesion refers to the process by which chromatin-associated cohesin becomes cohesion-competent. (wikipedia.org)
Cohesin must undergo subsequent modification ("establishment") to be capable of physically holding the sister chromosomes together. (wikipedia.org)
Tying establishment to DNA replication allows the cell to institute cohesion as soon as the sister chromatids are formed. (wikipedia.org)
The Eco1/Ctf7 gene (yeast) was one of the first genes to be identified as specifically required for the establishment of cohesion. (wikipedia.org)
Though Eco1 contains several functional domains, it is the acetyltransferase activity of the protein which is crucial for establishment of cohesion. (wikipedia.org)
The Pds5 gene was also identified in yeast as necessary for the establishment of cohesion. (wikipedia.org)
Pds5 is not strictly establishment-specific, as Pds5 is necessary for maintenance of cohesion during G2 and M phase. (wikipedia.org)
One model of establishment of cohesion suggests that establishment is mediated by the replacement of Wapl in the Wapl-Pds5-cohesin complex with the Sororin protein. (wikipedia.org)
Such a gating mechanism, if reversible, might hold the key to unlocking several apparent paradoxes involving cohesin deposition versus sister pairing (see An integrated view of cohesion establishment). (rupress.org)
PCNA controls establishment of sister chromatid cohesion during S phase. (ihcworld.com)
Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. (silverchair.com)
His study in Genetics concentrates on Establishment of sister chromatid cohesion, Meiosis, Centromere, Chromosome segregation and Origin recognition complex. (research.com)
His research in Establishment of sister chromatid cohesion intersects with topics in Meiosis II, Spindle apparatus and Kinetochore. (research.com)
Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. (cell-stress.com)
The RFCCtf18 variant complex is required for activation of the intra‐S‐phase checkpoint at stalled replication forks and aids the establishment of sister chromatid cohesion. (diamond.ac.uk)

We show here that the yeast homologue of Spo76, called Pds5, is essential for establishing sister chromatid cohesion and maintaining it during metaphase. (nih.gov)

Miller CLW and Winston F (2023) The conserved histone chaperone Spt6 is strongly required for DNA replication and genome stability. (yeastgenome.org)
All of his Genetics and Genome, Gene, DNA re-replication, Aurora B kinase and Polyploid investigations are sub-components of the entire Genetics study. (research.com)
Collectively, our results suggest that the deposition by CAF-1 of newly-synthesized H3-H4 histones during DNA replication creates a chromatin environment that favors sister chromatid cohesion and maintains genome integrity. (cell-stress.com)
Cohesin has a dual role, as it not only holds together sister DNAs but also builds the DNA loops that shape the interphase genome. (cbinsights.com)
While each DNA blueprint, or gene, encodes for a different machine or structure, the genome, the collection of DNA wrapped up inside the nucleus, is much more active than a quiet library of neatly stacked blue-prints. (birmingham.ac.uk)
We examine the impact that processes such as transcription and replication have on genome stability. (birmingham.ac.uk)
The human papillomavirus (HPV) E2 protein is a multifunctional protein essential for the control of virus gene expression, genome replication and persistence. (microbiologyresearch.org)
SMC5/6 acts jointly with Fanconi anemia factors to support DNA repair and genome stability. (ifom.eu)

A quite separate protein called Spo76 is required for sister chromatid cohesion during meiosis in the ascomycete Sordaria. (nih.gov)
Enduring and robust, structural cohesins resist poleward-pulling forces produced by the mitotic spindle that act to separate sister chromatids and must often persist for extended periods of time in meiosis. (rupress.org)
Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I. (ox.ac.uk)
During meiosis, two rounds of chromosome segregation occur after a single round of DNA replication, producing haploid progeny from diploid progenitors. (ox.ac.uk)
Cdc5 is thus required both for the formation of chiasmata and for cosegregation of sister centromeres at meiosis I. (ox.ac.uk)

Cohesion is then maintained until the point when chromosomes line up in the middle of the cell. (sciencedaily.com)
Sister chromatid cohesion is necessary for the equal segregation of chromosomes and subsequent genomic inheritance. (sciencedaily.com)
Our identification of a protein that acts both to establish and protect cohesion in Drosophila chromosomes may represent an intermediate stage of the evolutionary inheritance of factors involved in maintaining genomic integrity. (sciencedaily.com)
Building chromosomes without bricks: Has the textbook model of DNA compaction into chromosomes been upended? (elsevierpure.com)
In order to provide each daughter cell with the exact right set of 46 chromosomes, the sister chromatids are stably entrapped by large, circular protein complex named cohesins. (amsterdamumc.org)
the process that duplicated chromosomes (the sister chromatids) remain connected from the time of their synthesis in S-phase until their separation in anaphase, to allow the proper distribution of DNA over two new daughter cells. (amsterdamumc.org)
The protection of centromeric cohesin by SGO1 maintains the sister chromatid cohesion that resists the pulling forces of microtubules until all chromosomes are attached in a bipolar manner to the mitotic spindle. (cbinsights.com)
Cohesion at centromeres is protected by Shugoshin (SGO1) 11 , 12 , 13 , 14 , giving rise to the typical X-shaped structure of human chromosomes. (cbinsights.com)
In addition, I propose to investigate how chromosome condensation and cohesion influence the dynamics of chromosome segregation and how (if) cells adapt when in the presence of abnormal chromosomes. (europa.eu)
First, crossovers between maternal and paternal sister chromatids (detected cytologically as chiasmata) bind replicated maternal and paternal chromosomes together. (ox.ac.uk)

Loads PCNA onto primed templates regulating velocity, spacing and restart activity of replication forks. (nih.gov)
Prevention of unwanted recombination at damaged replication forks. (ifom.eu)
The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks. (ifom.eu)
Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage. (nih.gov)

Eco1 interacts with many proteins directly involved in DNA replication, including the processivity clamp PCNA, clamp loader subunits, and a DNA helicase. (wikipedia.org)
To execute these functions, the replisome contains a helicase, DNA polymerases, as well as several associated factors that together make up the replication fork (see Figure 1). (advancedsciencenews.com)
Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase-Pol ε Interaction. (yeastgenome.org)
How does the DNA helicase DDX11 (mutated in the cohesinopathy Warsaw Breakage Syndrome) contribute to replication fork progression, sister chromatid cohesion and DNA damage response? (amsterdamumc.org)
Timeless couples G-quadruplex detection with processing by DDX11 helicase during DNA replication. (ifom.eu)

CHTF18 (MIM 613201), CHTF8 (MIM 613202), and DSCC1 are components of an alternative replication factor C (RFC) (see MIM 600404) complex that loads PCNA (MIM 176740) onto DNA during S phase of the cell cycle (Merkle et al. (nih.gov)
Synthesis of the nuclear protein cyclin (PCNA) and its relationship with DNA replication. (ihcworld.com)
PCNA recruits cohesin loader Scc2 to ensure sister chromatid cohesion. (ifom.eu)

For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)

This solves the problem of how the cell might properly identify and pair sister chromatids by ensuring that the sister chromatids are never separate once replication has occurred. (wikipedia.org)
A key issue is how cells pair sister chromatids but preclude the catastrophic pairing of nonsister chromatids. (rupress.org)

Cohesion is established during DNA replication, is partially dismantled in many, but not all, organisms during prophase, and is finally destroyed at the metaphase-to-anaphase transition. (nih.gov)
At the metaphase-anaphase transition, cohesion is dissolved and sisters segregate to opposite poles via microtubule-dependent movements. (silverchair.com)
Terry L. Orr-Weaver focuses mostly in the field of Sister chromatids, narrowing it down to matters related to Cohesin and, in some cases, Anaphase. (research.com)
His work in Sister chromatids addresses issues such as Anaphase, which are connected to fields such as Metaphase. (research.com)
Terry L. Orr-Weaver mostly deals with Genetics, Cell biology, Embryo, Anaphase-promoting complex and DNA replication. (research.com)
It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. (maayanlab.cloud)
Third, sister chromatid cohesion near centromeres is preserved at anaphase I when cohesion along chromosome arms is destroyed. (ox.ac.uk)

Our functional studies of selected CIN genes in yeast have elucidated mechanistic insights into various aspects of the chromosome cycle, including sister chromatid cohesion, kinetochores, DNA replication and repair, and cell cycle checkpoints. (ubc.ca)
Second, sister kinetochores attach to microtubules from the same pole (mono-polar orientation), causing maternal and paternal centromere pairs (and not sister chromatids) to be separated. (ox.ac.uk)
They also fail to properly localize the Lrs4 (ref. 3) and Mam1 (ref. 4) monopolin proteins, resulting in bipolar orientation of sister kinetochores. (ox.ac.uk)

At least two classes of factors are critical for sister chromatid pairing: structural cohesins and deposition factors. (rupress.org)

In addition to interacting with cohesin, Pds5 also interacts with Wapl (wings apart-like), another protein that has been implicated in the regulation of sister chromatid cohesion. (wikipedia.org)
May couple DNA replication to sister chromatid cohesion through regulation of the acetylation of the cohesin subunit SMC3. (nih.gov)
The Yokomori laboratory investigates the mechanisms of chromosome structural organization and how they affect DNA repair and gene regulation in human health and disease. (uci.edu)
Can we identify novel drug targets or synergistic drug combinations for tumor cells in which cohesion regulation is impaired? (amsterdamumc.org)

In particular, our research program aims to understand the execution, interplay, and coordination of DNA replication and repair, sister-chromatid cohesion, and chromosome segregation during the cell cycle. (packard.org)
This will increase our understanding of the complex interplay between sister chromatid cohesion and DNA replication, and may provide clinical opportunities if specific vulnerabilities of cancer cells with defective cohesion can be found and targeted. (amsterdamumc.org)

In eukaryotes, DNA replication is separated in time from chromosome segregation. (rupress.org)
By protecting centromeric cohesion, SGO1 thus ensures faithful chromosome segregation. (cbinsights.com)
This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. (nih.gov)

DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7. (yeastgenome.org)

Figure 1: Schematic representation of the eukaryotic replication fork. (advancedsciencenews.com)

Here we examined the genetic interaction between the heterotrimeric chromatin assembly factor-1 (CAF-1), a central component of chromatin assembly during replication, and the core replisome component Ctf4. (cell-stress.com)
We find that CAF-1 deficient cells as well as cells affected in newly-synthesized H3-H4 histones deposition during DNA replication exhibit a severe negative growth with ctf4 ∆ mutant. (cell-stress.com)
In the absence of CTF4 , CAF-1 is essential for viability in cells experiencing replication problems, in cells lacking functional S-phase checkpoint or functional spindle checkpoint, and in cells lacking DNA repair pathways involving homologous recombination. (cell-stress.com)
We present evidence that CAF-1 affects cohesin association to chromatin in a DNA-damage-dependent manner and is essential to maintain cohesion in the absence of CTF4 . (cell-stress.com)
Loss of CTF4, encoding a replisome component involved in sister chromatid cohesion, also suppresses hst3 hst4 phenotypes. (nyu.edu)

Bryant JA and Aves SJ (2011) Initiation of DNA replication: functional and evolutionary aspects. (yeastgenome.org)

Eco1 must be present in S phase to establish cohesion, but its continued presence is not required to maintain cohesion. (wikipedia.org)

As a member of one scientific family, Terry L. Orr-Weaver mostly works in the field of DNA replication, focusing on DNA repair and, on occasion, Origin of replication and G2-M DNA damage checkpoint. (research.com)
Here we show that cells lacking Hst3p and Hst4p, in which H3 K56 is constitutively hyperacetylated, exhibit hallmarks of spontaneous DNA damage, such as activation of the checkpoint kinase Rad53p and upregulation of DNA-damage inducible genes. (nyu.edu)

Chromosomal DNA replication involves several complex protein complexes. (advancedsciencenews.com)
In the random mobilization/loading model, cohesin is stochastically removed from unreplicated chromatin and unrelated cohesin complexes are independently loaded in replicated DNA duplexes (Fig. 3a). (advancedsciencenews.com)
Replication factor C complexes load and unload processivity clamps from DNA and are involved in multiple DNA replication and repair pathways. (diamond.ac.uk)
Cohesin complexes have a dynamic mode of DNA binding that involves DNA entrapment and release. (cbinsights.com)

In vertebrate cells, sister chromatids are associated along their length from their formation in S phase through metaphase. (silverchair.com)
The resulting sister chromatid cohesion allows sister chromatids to be orderly aligned in metaphase and attached to microtubules from opposite poles. (amsterdamumc.org)

Finally, our data indicate that the CAF-1-dependent pathway required for cohesion is functionally distinct from the Rtt101-Mms1-Mms22 pathway which functions in replicated chromatin assembly. (cell-stress.com)

The various areas that Terry L. Orr-Weaver examines in his Cell cycle study include Transcription factor and DNA replication. (research.com)
His Origin recognition complex study incorporates themes from General transcription factor, Pre-replication complex, Control of chromosome duplication, Licensing factor and E-box. (research.com)
The compact architecture of heterochromatin limits the accessibility of the transcription machinery to the embedded DNA, thereby silencing gene expression. (biomedcentral.com)
Accordingly, H3K9me3-dependent heterochromatin is considered as a barrier to cell fate changes, by preventing some transcription factors to bind DNA [ 18 ]. (biomedcentral.com)
Using cell-based assays, we show that co-expression of L1 and E2 results in enhanced transcription and virus origin-dependent DNA replication. (microbiologyresearch.org)

Moreover, the behavior of Dmt and its means of establishing cohesion were very similar to that of vertebrate sororin. (sciencedaily.com)
Vertebrate CTF18 and DDX11 essential function in cohesion is bypassed by preventing WAPL-mediated cohesin release. (ifom.eu)

Cohesion proteins SMC1ß, SMC3, REC8 and STAG3 appear to participate in the cohesion of sister chromatids throughout the meiotic process in human oocytes. (wikipedia.org)
The finding that destruction of mitotic cohesion is regulated by Polo-like kinases prompted us to investigate the meiotic role of the yeast Polo-like kinase Cdc5. (ox.ac.uk)

Under this problem, p53-positive cells exhibited arrest in the G1 stage, whereas p53-null cells inserted the S stage and dropped their viability due to the deposition of DNA harm, recommending that MCMBP is certainly a potential focus on for eliminating p53-deficient malignancies. (treatmentforprostatecancer.info)

Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. (yeastgenome.org)

Furthermore, we describe genetic interactions between CAF-1 and essential genes involved in cohesin loading, cohesin stabilization, and cohesin component indicating that CAF-1 is crucial for viability when sister chromatid cohesion is affected. (cell-stress.com)
Consistently, hst3 hst4 cells display synthetic lethality interactions with mutations that cripple genes involved in DNA replication and DNA double-strand break (DSB) repair. (nyu.edu)
The way the DNA is structured, wrapped and read is fundamental to how and when the blueprint genes are read. (birmingham.ac.uk)

Dukaj L and Rhind N (2021) The capacity of origins to load MCM establishes replication timing patterns. (yeastgenome.org)

The identification of both replication factor C and DNA helicases as critical for sister chromatid pairing has brought new insights into this fundamental process. (rupress.org)

Sister chromatid cohesion depends on a complex called cohesin, which contains at least four subunits: Smc1, Smc3, Scc1 and Scc3. (nih.gov)
Cohesin entraps DNA inside its ring-shaped structure 4 , which at its core consists of SMC1, SMC3 and SCC1 (also known as RAD21 or Mcd1). (cbinsights.com)

As cohesin is already present before the arrival of the replication fork, the question arises how cohesin interacts with the replisome. (advancedsciencenews.com)
Figure 3: Different models showing the intefacing between chromatin-bound cohesin and the replication fork. (advancedsciencenews.com)
How are cohesin dynamics regulated in the context of a normally progressing DNA replication fork, and in conditions of DNA replication stress? (amsterdamumc.org)

The proper copying and repair of DNA to maintain the correct sequence and structure of genomes is critical to the proper function of cells, and repair and replication is frequently disrupted in cancers and targeted by cancer treatments. (birmingham.ac.uk)
Our research is defining the normal mechanisms of DNA replication and repair, with the aim of understanding how it is deregulated in cancer cells. (birmingham.ac.uk)
In addition, in some patients with a personal or family history of breast and ovarian cancer, the protective role of BRCA1 in DNA-copying is disabled - while its break repair function is still active. (birmingham.ac.uk)
The disorders are characterized by a defect in DNA repair mechanisms or genomic instability, and patients with these disorders show increased predisposition to cancer. (medscape.com)

In vertebrates, this protection is provided by the shugoshin protein, but mechanisms of Drosophila cohesion protection were unclear. (sciencedaily.com)
Now, Japanese researchers at Nagoya University have identified Dalmatian (Dmt) as a fruit fly protein related to sororin that is both required for cohesion and has shugoshin-like cohesion protection roles. (sciencedaily.com)

This new complex is the established, cohesion-competent cohesin state. (wikipedia.org)
Sequence similarities and secondary structure predictions indicate that Pds5 consists of tandemly repeated HEAT repeats, and might therefore function as a protein-protein interaction scaffold, possibly in the cohesin-DNA complex assembly. (nih.gov)
Specifically, we use various DNA damaging methods, including laser microirradiation to study nucleus-wide epigenetic responses to complex DNA damage through PARP signaling and metabolic alteration. (uci.edu)
Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. (silverchair.com)
However, Pds5p and the cohesin complex likely have distinct roles in cohesion. (silverchair.com)
Functional control of Eco1 through the MCM complex in sister chromatid cohesion. (yeastgenome.org)
Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. (yeastgenome.org)
Terry L. Orr-Weaver spends much of his time researching Cell biology, Genetics, Embryo, DNA replication and Origin recognition complex. (research.com)
I am interested in how cells organize and transfer their DNA, how deregulation of these complex mechanisms affect cell fate and diseases such as cancer, and how we may be able to exploit the understanding to identify footholds for therapeutic benefit. (amsterdamumc.org)

We identified SMT4 , which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. (silverchair.com)

In our lab, we try to answer questions such as: how does oncogenic transformation affect sister chromatid cohesion? (amsterdamumc.org)
Comparison of the structure and DNA-binding properties of the E2 proteins from an oncogenic and a non-oncogenic human papillomavirus. (microbiologyresearch.org)

18292778 ). HDAC3 plays a crucial role in DNA replication and DNA damage control. (iiserpune.ac.in)

Early data suggesting that S phase is crucial to cohesion was based on the fact that after S phase, sister chromatids are always found in the bound state. (wikipedia.org)
Additionally, the research team found that blocking Dmt gene expression prevented cohesion from occurring, showing that Dmt is crucial for the launch of cohesion. (sciencedaily.com)

These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion. (silverchair.com)

Sororin also has chromatin binding activity independent of its ability to mediate cohesion. (wikipedia.org)
This typically occurs during DNA replication, and in vertebrates requires the cohesin-associating protein sororin. (sciencedaily.com)

Dmt localizes to regions of tightly packed chromatin through interactions with other proteins to launch cohesion, and protects cohesion at other cell cycle timepoints by binding different proteins. (sciencedaily.com)
Exploring cohesin and replisome interactions during DNA replication. (advancedsciencenews.com)
Changing protein-DNA interactions promote ORC binding-site exchange during replication origin licensing. (yeastgenome.org)
Promoters, enhancers and physical interactions between regions of DNA are important in ways that are only now becoming apparent, directing phases of development, and often perturbed in cancers. (birmingham.ac.uk)

Anatomy27

Organisms17

Diseases10

Chemicals and Drugs97

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes90

Information Science4

Health Care2

Mitosis13

Establishment16

Essential for establishing sister chrom1

Genome8

Meiosis5

Chromosomes10

Forks4

Helicase5

PCNA3

Progression1

Pair sister chromatids2

Anaphase7

Kinetochores3

Cohesins1

Regulation4

Interplay2

Segregation3

Regulates1

Eukaryotic replication1

Ctf45

Initiation of DNA replication1

Maintain cohesion1

Checkpoint2

Complexes4

Metaphase2

Chromatin assembly1

Transcription5

Vertebrate2

Meiotic2

Deposition1

Saccharomyces1

Genes3

20211

Helicases1

SMC32

Fork3

Repair4

Shugoshin2

Complex9

Pds51

Oncogenic2

Damage1

Crucial2

Promotes1

Sororin2

Interactions4