scholarly journals MCM2–7-dependent cohesin loading during S phase promotes sister-chromatid cohesion

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ge Zheng ◽  
Mohammed Kanchwala ◽  
Chao Xing ◽  
Hongtao Yu
Keyword(s):  
Sister Chromatid ◽  
Replication Fork ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Nucleosome Assembly ◽  
Okazaki Fragment ◽  
Replicative Helicase ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Okazaki Fragment Processing

DNA replication transforms cohesin rings dynamically associated with chromatin into the cohesive form to establish sister-chromatid cohesion. Here, we show that, in human cells, cohesin loading onto chromosomes during early S phase requires the replicative helicase MCM2–7 and the kinase DDK. Cohesin and its loader SCC2/4 (NIPBL/MAU2 in humans) associate with DDK and phosphorylated MCM2–7. This binding does not require MCM2–7 activation by CDC45 and GINS, but its persistence on activated MCM2–7 requires fork-stabilizing replisome components. Inactivation of these replisome components impairs cohesin loading and causes interphase cohesion defects. Interfering with Okazaki fragment processing or nucleosome assembly does not impact cohesion. Therefore, MCM2–7-coupled cohesin loading promotes cohesion establishment, which occurs without Okazaki fragment maturation. We propose that the cohesin–loader complex bound to MCM2–7 is mobilized upon helicase activation, transiently held by the replisome, and deposited behind the replication fork to encircle sister chromatids and establish cohesion.

scholarly journals Multivalent interaction of ESCO2 with the replication machinery is required for sister chromatid cohesion in vertebrates

2019 ◽  
Vol 117 (2) ◽  
pp. 1081-1089 ◽  
Author(s):  
Dawn Bender ◽  
Eulália Maria Lima Da Silva ◽  
Jingrong Chen ◽  
Annelise Poss ◽  
Lauren Gawey ◽  
...  
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Replication Machinery ◽  
Replicative Helicase ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
N Terminus ◽  
Mcm Complex ◽  
Unique Ability

The tethering together of sister chromatids by the cohesin complex ensures their accurate alignment and segregation during cell division. In vertebrates, sister chromatid cohesion requires the activity of the ESCO2 acetyltransferase, which modifies the Smc3 subunit of cohesin. It was shown recently that ESCO2 promotes cohesion through interaction with the MCM replicative helicase. However, ESCO2 does not significantly colocalize with the MCM complex, suggesting there are additional interactions important for ESCO2 function. Here we show that ESCO2 is recruited to replication factories, sites of DNA replication, through interaction with PCNA. We show that ESCO2 contains multiple PCNA-interaction motifs in its N terminus, each of which is essential to its ability to establish cohesion. We propose that multiple PCNA-interaction motifs embedded in a largely flexible and disordered region of the protein underlie the unique ability of ESCO2 to establish cohesion between sister chromatids precisely as they are born during DNA replication.

scholarly journals RFCCtf18 and the Swi1-Swi3 Complex Function in Separate and Redundant Pathways Required for the Stabilization of Replication Forks to Facilitate Sister Chromatid Cohesion in Schizosaccharomyces pombe

2008 ◽  
Vol 19 (2) ◽  
pp. 595-607 ◽  
Author(s):  
Alison B. Ansbach ◽  
Chiaki Noguchi ◽  
Ian W. Klansek ◽  
Mike Heidlebaugh ◽  
Toru M. Nakamura ◽  
...  
Keyword(s):  
Stress Response ◽  
Fission Yeast ◽  
Sister Chromatid ◽  
Replication Fork ◽  
Complex Function ◽  
Dna Helicase ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion ◽  
Factor C

Sister chromatid cohesion is established during S phase near the replication fork. However, how DNA replication is coordinated with chromosomal cohesion pathway is largely unknown. Here, we report studies of fission yeast Ctf18, a subunit of the RFCCtf18 replication factor C complex, and Chl1, a putative DNA helicase. We show that RFCCtf18 is essential in the absence of the Swi1–Swi3 replication fork protection complex required for the S phase stress response. Loss of Ctf18 leads to an increased sensitivity to S phase stressing agents, a decreased level of Cds1 kinase activity, and accumulation of DNA damage during S phase. Ctf18 associates with chromatin during S phase, and it is required for the proper resumption of replication after fork arrest. We also show that chl1Δ is synthetically lethal with ctf18Δ and that a dosage increase of chl1+ rescues sensitivities of swi1Δ to S phase stressing agents, indicating that Chl1 is involved in the S phase stress response. Finally, we demonstrate that inactivation of Ctf18, Chl1, or Swi1-Swi3 leads to defective centromere cohesion, suggesting the role of these proteins in chromosome segregation. We propose that RFCCtf18 and the Swi1–Swi3 complex function in separate and redundant pathways essential for replication fork stabilization to facilitate sister chromatid cohesion in fission yeast.

scholarly journals SOLO: a meiotic protein required for centromere cohesion, coorientation, and SMC1 localization in Drosophila melanogaster

2010 ◽  
Vol 188 (3) ◽  
pp. 335-349 ◽  
Author(s):  
Rihui Yan ◽  
Sharon E. Thomas ◽  
Jui-He Tsai ◽  
Yukihiro Yamada ◽  
Bruce D. McKee
Keyword(s):  
Drosophila Melanogaster ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Early Prophase ◽  
Wild Type ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Mutant Phenotypes ◽  
Meiosis I ◽  
Novel Protein

Sister chromatid cohesion is essential to maintain stable connections between homologues and sister chromatids during meiosis and to establish correct centromere orientation patterns on the meiosis I and II spindles. However, the meiotic cohesion apparatus in Drosophila melanogaster remains largely uncharacterized. We describe a novel protein, sisters on the loose (SOLO), which is essential for meiotic cohesion in Drosophila. In solo mutants, sister centromeres separate before prometaphase I, disrupting meiosis I centromere orientation and causing nondisjunction of both homologous and sister chromatids. Centromeric foci of the cohesin protein SMC1 are absent in solo mutants at all meiotic stages. SOLO and SMC1 colocalize to meiotic centromeres from early prophase I until anaphase II in wild-type males, but both proteins disappear prematurely at anaphase I in mutants for mei-S332, which encodes the Drosophila homologue of the cohesin protector protein shugoshin. The solo mutant phenotypes and the localization patterns of SOLO and SMC1 indicate that they function together to maintain sister chromatid cohesion in Drosophila meiosis.

scholarly journals Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion

PLoS Genetics ◽  
2018 ◽  
Vol 14 (10) ◽  
pp. e1007622 ◽  
Author(s):  
Giuseppe Cortone ◽  
Ge Zheng ◽  
Pasquale Pensieri ◽  
Viviana Chiappetta ◽  
Rosarita Tatè ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Replication Fork ◽  
Dna Helicase ◽  
Sister Chromatid Cohesion ◽  
Protection Factor ◽  
Chromatid Cohesion

scholarly journals PCNA Controls Establishment of Sister Chromatid Cohesion during S Phase

2006 ◽  
Vol 23 (5) ◽  
pp. 723-732 ◽  
Author(s):  
George-Lucian Moldovan ◽  
Boris Pfander ◽  
Stefan Jentsch
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion

scholarly journals Hst3 Is Regulated by Mec1-dependent Proteolysis and Controls the S Phase Checkpoint and Sister Chromatid Cohesion by Deacetylating Histone H3 at Lysine 56

2007 ◽  
Vol 282 (52) ◽  
pp. 37805-37814 ◽  
Author(s):  
Safia Thaminy ◽  
Benjamin Newcomb ◽  
Jessica Kim ◽  
Tonibelle Gatbonton ◽  
Eric Foss ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Histone H3 ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion ◽  
S Phase Checkpoint

scholarly journals Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1β and SMC3

2003 ◽  
Vol 160 (5) ◽  
pp. 657-670 ◽  
Author(s):  
Maureen Eijpe ◽  
Hildo Offenberg ◽  
Rolf Jessberger ◽  
Ekaterina Revenkova ◽  
Christa Heyting
Keyword(s):  
Synaptonemal Complex ◽  
Sister Chromatid ◽  
Meiotic Prophase ◽  
S Phase ◽  
Synaptonemal Complexes ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Axial Element ◽  
Striking Contrast ◽  
Metaphase I

In meiotic prophase, the sister chromatids of each chromosome develop a common axial element (AE) that is integrated into the synaptonemal complex (SC). We analyzed the incorporation of sister chromatid cohesion proteins (cohesins) and other AE components into AEs. Meiotic cohesin REC8 appeared shortly before premeiotic S phase in the nucleus and formed AE-like structures (REC8-AEs) from premeiotic S phase on. Subsequently, meiotic cohesin SMC1β, cohesin SMC3, and AE proteins SCP2 and SCP3 formed dots along REC8-AEs, which extended and fused until they lined REC8-AEs along their length. In metaphase I, SMC1β, SMC3, SCP2, and SCP3 disappeared from the chromosome arms and accumulated around the centromeres, where they stayed until anaphase II. In striking contrast, REC8 persisted along the chromosome arms until anaphase I and near the centromeres until anaphase II. We propose that REC8 provides a basis for AE formation and that the first steps in AE assembly do not require SMC1β, SMC3, SCP2, and SCP3. Furthermore, SMC1β, SMC3, SCP2, and SCP3 cannot provide arm cohesion during metaphase I. We propose that REC8 then provides cohesion. RAD51 and/or DMC1 coimmunoprecipitates with REC8, suggesting that REC8 may also provide a basis for assembly of recombination complexes.

scholarly journals Chromosome interaction over a distance in meiosis

2015 ◽  
Vol 2 (2) ◽  
pp. 150029 ◽  
Author(s):  
Mary Brady ◽  
Leocadia V. Paliulis
Keyword(s):  
Cell Division ◽  
Sex Chromosomes ◽  
Sister Chromatid ◽  
Daughter Cell ◽  
Sister Chromatid Cohesion ◽  
Sister Chromatids ◽  
Physical Connection ◽  
Chromatid Cohesion ◽  
Different Types ◽  
Random Segregation

The challenge of cell division is to distribute partner chromosomes (pairs of homologues, pairs of sex chromosomes or pairs of sister chromatids) correctly, one into each daughter cell. In the ‘standard’ meiosis, this problem is solved by linking partners together via a chiasma and/or sister chromatid cohesion, and then separating the linked partners from one another in anaphase; thus, the partners are kept track of, and correctly distributed. Many organisms, however, properly separate chromosomes in the absence of any obvious physical connection, and movements of unconnected partner chromosomes are coordinated at a distance. Meiotic distance interactions happen in many different ways and in different types of organisms. In this review, we discuss several different known types of distance segregation and propose possible explanations for non-random segregation of distance-segregating chromosomes.

scholarly journals A conserved activity for cohesin in bridging DNA molecules

2019 ◽  
Author(s):  
Pilar Gutierrez-Escribano ◽  
Matthew D. Newton ◽  
Aida Llauró ◽  
Jonas Huber ◽  
Loredana Tanasie ◽  
...  
Keyword(s):  
Single Molecule ◽  
Sister Chromatid ◽  
Regulation Of Gene Expression ◽  
Sister Chromatid Cohesion ◽  
Dna Molecules ◽  
Chromosome Architecture ◽  
Physiological Conditions ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Core Activity

AbstractEssential processes such as accurate chromosome segregation, regulation of gene expression and DNA repair rely on protein-mediated DNA tethering. Sister chromatid cohesion requires the SMC complex cohesin to act as a protein linker that holds replicated chromatids together (1, 2). The molecular mechanism by which cohesins hold sister chromatids has remained controversial. Here, we used a single molecule approach to visualise the activity of cohesin complexes as they hold DNA molecules. We describe a DNA bridging activity that requires ATP and is conserved from yeast to human cohesin. We show that cohesin can form two distinct classes of bridges at physiological conditions, a “permanent bridge” able to resists high force (over 80pN) and a “reversible bridge” that breaks at lower forces (5-40pN). Both classes of bridges require Scc2/Scc4 in addition to ATP. We demonstrate that bridge formation requires physical proximity of the DNA segments to be tethered and show that “permanent” cohesin bridges can move between two DNA molecules but cannot be removed from DNA when they occur in cis. This suggests that separate physical compartments in cohesin molecules are involved in the bridge. Finally, we show that cohesin tetramers, unlike condensin, cannot compact linear DNA molecules against low force, demonstrating that the core activity of cohesin tetramers is bridging DNA rather than compacting it. Our findings carry important implications for the understanding of the basic mechanisms behind cohesin-dependent establishment of sister chromatid cohesion and chromosome architecture.

Sign in / Sign up

Export Citation Format

Share Document