scholarly journals The acetyltransferase Eco1 elicits cohesin dimerization during S phase

2020 ◽  
Author(s):  
Di Shi ◽  
Shuaijun Zhao ◽  
Mei-Qing Zuo ◽  
Jingjing Zhang ◽  
Wenya Hou ◽  
...  
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Repair Gene ◽  
Additional Layer ◽  
Ring Model ◽  
Dna Repair Gene ◽  
Chromatid Cohesion

AbstractSister chromatid cohesion is established by Eco1 in S phase. Nevertheless, the exact consequence of Eco1-catalyzed acetylation is unknown, and the cohesive state remains highly controversial. Here we show that self-interactions of cohesin subunits Scc1/Rad21 and Scc3 occur in a DNA replication-coupled manner in both yeast and human. Through cross-linking mass spectrometry and VivosX analysis of purified cohesin, we show that a subpopulation of cohesin may exist as dimers. Importantly, cohesin-cohesin interaction becomes significantly compromised when Eco1 is depleted. On the other hand, deleting either deacetylase Hos1 or Eco1 antagonist Wpl1/Rad61 results in an increase (e.g., from ∼20% to 40%) of cohesin dimers. These findings suggest that cohesin dimerization is controlled by common mechanisms as the cohesion cycle, thus providing an additional layer of regulation for cohesin to execute various functions such as sister chromatid cohesion, DNA repair, gene expression, chromatin looping and high-order organization.Author SummaryCohesin is a ring that tethers sister chromatids since their synthesis during S phase till their separation in anaphase. According to the single-ring model, one ring holds twin sisters. Here we show a conserved cohesin-cohesin interaction from yeast to human. A subpopulation of cohesin is dimerized concomitantly with DNA replication. Cohesin dimerization is dependent on the acetyltransferase Eco1 and counteracted by the anti-establishment factor Wpl1 and deacetylase Hos1. Approximately 20% of cellular cohesin complexes are measured to be dimers, close to the level of Smc3 acetylation by Eco1 in vivo. These findings provide evidence to support the double-ring model in sister chromatid cohesion.

scholarly journals The acetyltransferase Eco1 elicits cohesin dimerization during S phase

2020 ◽  
Vol 295 (22) ◽  
pp. 7554-7565 ◽  
Author(s):  
Di Shi ◽  
Shuaijun Zhao ◽  
Mei-Qing Zuo ◽  
Jingjing Zhang ◽  
Wenya Hou ◽  
...  
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Cross Linking ◽  
Temperature Sensitive ◽  
Exact Nature ◽  
Chromatid Cohesion ◽  
Lysine Residues

Cohesin is a DNA-associated protein complex that forms a tripartite ring controlling sister chromatid cohesion, chromosome segregation and organization, DNA replication, and gene expression. Sister chromatid cohesion is established by the protein acetyltransferase Eco1, which acetylates two conserved lysine residues on the cohesin subunit Smc3 and thereby ensures correct chromatid separation in yeast (Saccharomyces cerevisiae) and other eukaryotes. However, the consequence of Eco1-catalyzed cohesin acetylation is unknown, and the exact nature of the cohesive state of chromatids remains controversial. Here, we show that self-interactions of the cohesin subunits Scc1/Rad21 and Scc3 occur in a DNA replication–coupled manner in both yeast and human cells. Using cross-linking MS-based and in vivo disulfide cross-linking analyses of purified cohesin, we show that a subpopulation of cohesin may exist as dimers. Importantly, upon temperature-sensitive and auxin-induced degron-mediated Eco1 depletion, the cohesin-cohesin interactions became significantly compromised, whereas deleting either the deacetylase Hos1 or the Eco1 antagonist Wpl1/Rad61 increased cohesin dimer levels by ∼20%. These results indicate that cohesin dimerizes in the S phase and monomerizes in mitosis, processes that are controlled by Eco1, Wpl1, and Hos1 in the sister chromatid cohesion-dissolution cycle. These findings suggest that cohesin dimerization is controlled by the cohesion cycle and support the notion that a double-ring cohesin model operates in sister chromatid cohesion.

scholarly journals Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity in Drosophila

2019 ◽  
Author(s):  
Michelle Pherson, ◽  
Ziva Misulovin ◽  
Maria Gause ◽  
Dale Dorsett
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Gene Promoters ◽  
Replication Origins ◽  
Genome Wide ◽  
Chromatid Cohesion ◽  
Dna Replication Origin ◽  
Dna Replication Origins

AbstractCohesin consists of the Smc1-Smc3-Rad21 tripartite ring and the SA protein that interacts with Rad21. The Nipped-B protein loads cohesin topologically around chromosomes to mediate sister chromatid cohesion and facilitate long-range control of gene transcription. It is largely unknown how Nipped-B and cohesin associate specifically with gene promoters and transcriptional enhancers, or how sister chromatid cohesion is established. Here we use genome-wide chromatin immunoprecipitation in Drosophila cells to show that SA and the Fs(1)h (BRD4) BET domain protein help recruit Nipped-B and cohesin to enhancers and DNA replication origins, while the MED30 subunit of the Mediator complex directs Nipped-B and Rad21 to promoters. All enhancers and their neighboring promoters are close to DNA replication origins and bind SA with proportional levels of cohesin subunits. Most promoters are far from origins and lack SA, but bind Nipped-B and Rad21 with sub-proportional amounts of Smc1, indicating that they bind SA-deficient cohesin part of the time. Genetic data confirm that Nipped-B and Rad21 function together with Fs(1)h in vivo to facilitate Drosophila development. These findings demonstrate that Nipped-B and cohesin are differentially targeted to enhancers and promoters and suggest models for how SA and DNA replication help establish sister chromatid cohesion and facilitate enhancer-promoter communication. They indicate that SA is not an obligatory cohesin subunit but a factor that controls cohesin location on chromosomes.

scholarly journals Fission Yeast Eso1p Is Required for Establishing Sister Chromatid Cohesion during S Phase

2000 ◽  
Vol 20 (10) ◽  
pp. 3459-3469 ◽  
Author(s):  
Koichi Tanaka ◽  
Toshihiro Yonekawa ◽  
Yosuke Kawasaki ◽  
Mihoko Kai ◽  
Kanji Furuya ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Uv Irradiation ◽  
Sister Chromatid ◽  
Budding Yeast ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Terminal Region ◽  
Chromatid Cohesion ◽  
M Phase

ABSTRACT Sister chromatid cohesion is essential for cell viability. We have isolated a novel temperature-sensitive lethal mutant namedeso1-H17 that displays spindle assembly checkpoint-dependent mitotic delay and abnormal chromosome segregation. At the permissive temperature, the eso1-H17 mutant shows mild sensitivity to UV irradiation and DNA-damaging chemicals. At the nonpermissive temperature, the mutant is arrested in M phase with a viability loss due to a failure to establish sister chromatid cohesion during S phase. The lethal M-phase arrest phenotype, however, is suppressed by inactivation of a spindle checkpoint. Theeso1 + gene is not essential for the onset and progression of DNA replication but has remarkable genetic interactions with those genes regulating the G1-S transition and DNA replication. The N-terminal two-thirds of Eso1p is highly homologous to DNA polymerase η of budding yeast and humans, and the C-terminal one-third is homologous to budding yeast Eco1p (also called Ctf7p), which is required for the establishment of sister chromatid cohesion. Deletion analysis and determination of the mutation site reveal that the function of the Eco1p/Ctf7p-homologous domain is necessary and sufficient for sister chromatid cohesion. On the other hand, deletion of the DNA polymerase η domain in Eso1p increases sensitivity to UV irradiation. These results indicate that Eso1p plays a dual role during DNA replication. The C-terminal region acts to establish sister chromatid cohesion, and the N-terminal region presumably catalyzes translesion DNA synthesis when template DNA contains lesions that block regular DNA replication.

scholarly journals Cul4-Ddb1 ubiquitin ligases facilitate DNA replication-coupled sister chromatid cohesion through regulation of cohesin acetyltransferase Esco2

2018 ◽  
Author(s):  
Haitao Sun ◽  
Jiaxin Zhang ◽  
Jingjing Zhang ◽  
Zhen Li ◽  
Qinhong Cao ◽  
...  
Keyword(s):  
Dna Replication ◽  
Ubiquitin Ligase ◽  
Sister Chromatid ◽  
Critical Role ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
Sister Chromatid Cohesion ◽  
Vital Role ◽  
Chromatid Cohesion ◽  
Evolutionarily Conserved

AbstractCohesin acetyltransferases Esco1 and Esco2 play a vital role in establishing sister chromatid cohesion. How Esco1 and Esco2 are controlled to achieve this in a DNA replication-coupled manner remains unclear in higher eukaryotes. Here we show that Cul4-RING ligases (CRL4s) play a critical role in sister chromatid cohesion in human cells. Depletion of Cul4A, Cul4B or Ddb1 subunits substantially reduces normal cohesion efficiency. We also show that Mms22L, a vertebrate ortholog of yeast Mms22, is one of Ddb1 and Cul4-associated factors (DCAFs) involved in cohesion. Several lines of evidence suggest a selective interaction of CRL4s with Esco2, but not Esco1. Depletion of either CRL4s or Esco2 causes a defect in Smc3 acetylation which can be rescued by HDAC8 inhibition. More importantly, both CRL4s and PCNA act as mediators for efficiently stabilizing Esco2 on chromatin and catalyzing Smc3 acetylation. Taken together, we propose an evolutionarily conserved mechanism in which CRL4s and PCNA regulate Esco2-dependent establishment of sister chromatid cohesion.Author summaryWe identified human Mms22L as a substrate specific adaptor of Cul4-Ddb1 E3 ubiquitin ligase. Downregulation of Cul4A, Cul4B or Ddb1 subunit causes reduction of acetylated Smc3, via interaction with Esco2 acetyltransferase, and then impairs sister chromatid cohesion in 293T cells. We found functional complementation between Cul4-Ddb1-Mms22L E3 ligase and Esco2 in Smc3 acetylation and sister chromatid cohesion. Interestingly, both Cul4-Ddb1 E3 ubiquitin ligase and PCNA contribute to Esco2 mediated Smc3 acetylation. To summarise, we demonstrated an evolutionarily conserved mechanism in which Cul4-Ddb1 E3 ubiquitin ligases and PCNA regulate Esco2-dependent establishment of sister chromatid cohesion.

scholarly journals A Coordinated Temporal Interplay of Nucleosome Reorganization Factor, Sister Chromatin Cohesion Factor, and DNA Polymerase α Facilitates DNA Replication

2004 ◽  
Vol 24 (21) ◽  
pp. 9568-9579 ◽  
Author(s):  
Yanjiao Zhou ◽  
Teresa S.-F. Wang
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
S Phase ◽  
Terminal Region ◽  
Replication Complex ◽  
Dna Polymerase Α ◽  
Chromatid Cohesion ◽  
Phase Progression

ABSTRACT DNA replication depends critically upon chromatin structure. Little is known about how the replication complex overcomes the nucleosome packages in chromatin during DNA replication. To address this question, we investigate factors that interact in vivo with the principal initiation DNA polymerase, DNA polymerase α (Polα). The catalytic subunit of budding yeast Polα (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p. Here, we show that an N-terminal region of Polα (Pol1p) that is evolutionarily conserved among different species interacts with Spt16p-Pob3p and Ctf4p in vivo. A mutation in a glycine residue in this N-terminal region of POL1 compromises the ability of Pol1p to associate with Spt16p and alters the temporal ordered association of Ctf4p with Pol1p. The compromised association between the chromatin-reorganizing factor Spt16p and the initiating DNA polymerase Pol1p delays the Pol1p assembling onto and disassembling from the late-replicating origins and causes a slowdown of S-phase progression. Our results thus suggest that a coordinated temporal and spatial interplay between the conserved N-terminal region of the Polα protein and factors that are involved in reorganization of nucleosomes and promoting establishment of sister chromatin cohesion is required to facilitate S-phase progression.

scholarly journals Division of Labor between PCNA Loaders in DNA Replication and Sister Chromatid Cohesion Establishment

2020 ◽  
Vol 78 (4) ◽  
pp. 725-738.e4
Author(s):  
Hon Wing Liu ◽  
Céline Bouchoux ◽  
Mélanie Panarotto ◽  
Yasutaka Kakui ◽  
Harshil Patel ◽  
...  
Keyword(s):  
Dna Replication ◽  
Division Of Labor ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
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 Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome

2016 ◽  
Vol 63 (3) ◽  
pp. 371-384 ◽  
Author(s):  
Catarina P. Samora ◽  
Julie Saksouk ◽  
Panchali Goswami ◽  
Ben O. Wade ◽  
Martin R. Singleton ◽  
...  
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
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 The acetyltransferase activity of San stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner

2007 ◽  
Vol 177 (4) ◽  
pp. 587-597 ◽  
Author(s):  
Fajian Hou ◽  
Chih-Wen Chu ◽  
Xiangduo Kong ◽  
Kyoko Yokomori ◽  
Hui Zou
Keyword(s):  
Cell Cycle ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Independent Manner ◽  
Acetyltransferase Activity ◽  
Chromatid Cohesion ◽  
Interphase Cells ◽  
Gain Access

Proper sister chromatid cohesion is critical for maintaining genetic stability. San is a putative acetyltransferase that is important for sister chromatid cohesion in Drosophila melanogaster, but not in budding yeast. We showed that San is critical for sister chromatid cohesion in HeLa cells, suggesting that this mechanism may be conserved in metazoans. Furthermore, although a small fraction of San interacts with the NatA complex, San appears to mediate cohesion independently. San exhibits acetyltransferase activity in vitro, and its activity is required for sister chromatid cohesion in vivo. In the absence of San, Sgo1 localizes correctly throughout the cell cycle. However, cohesin is no longer detected at the mitotic centromeres. Furthermore, San localizes to the cytoplasm in interphase cells; thus, it may not gain access to chromosomes until mitosis. Moreover, in San-depleted cells, further depletion of Plk1 rescues the cohesion along the chromosome arms, but not at the centromeres. Collectively, San may be specifically required for the maintenance of the centromeric cohesion in mitosis.

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