scholarly journals Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery

1999 ◽  
Vol 13 (3) ◽  
pp. 307-319 ◽  
Author(s):  
R. V. Skibbens ◽  
L. B. Corson ◽  
D. Koshland ◽  
P. Hieter
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Mitotic Chromosome ◽  
Chromosome Structure ◽  
Sister Chromatid Cohesion ◽  
Replication Machinery ◽  
Chromatid 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 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 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 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

Organization of Chromosomal DNA by SMC Complexes

2019 ◽  
Vol 53 (1) ◽  
pp. 445-482 ◽  
Author(s):  
Stanislau Yatskevich ◽  
James Rhodes ◽  
Kim Nasmyth
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Chromosomal Dna ◽  
Chromosome Architecture ◽  
Chromatid Cohesion ◽  
Dna Translocases ◽  
Structural Maintenance Of Chromosomes

Structural maintenance of chromosomes (SMC) complexes are key organizers of chromosome architecture in all kingdoms of life. Despite seemingly divergent functions, such as chromosome segregation, chromosome maintenance, sister chromatid cohesion, and mitotic chromosome compaction, it appears that these complexes function via highly conserved mechanisms and that they represent a novel class of DNA translocases.

Colchicine promotes a change in chromosome structure without loss of sister chromatid cohesion in prometaphase I-arrested bivalents

Chromosoma ◽  
2001 ◽  
Vol 110 (7) ◽  
pp. 478-486 ◽  
Author(s):  
Eva Rodríguez ◽  
Maria Parra ◽  
Julio Rufas ◽  
José Suja
Keyword(s):  
Sister Chromatid ◽  
Chromosome Structure ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion

scholarly journals Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex

2005 ◽  
Vol 25 (13) ◽  
pp. 5445-5455 ◽  
Author(s):  
Göran O. Bylund ◽  
Peter M. J. Burgers
Keyword(s):  
Dna Replication ◽  
Dna Binding ◽  
Sister Chromatid ◽  
Protein A ◽  
Replication Protein A ◽  
Dna Binding Protein ◽  
Sister Chromatid Cohesion ◽  
Replication Protein ◽  
Single Stranded Dna ◽  
Chromatid Cohesion

ABSTRACT The replication clamp PCNA is loaded around DNA by replication factor C (RFC) and functions in DNA replication and repair. Regulated unloading of PCNA during the progression and termination of DNA replication may require additional factors. Here we show that a Saccharomyces cerevisiae complex required for the establishment of sister chromatid cohesion functions as an efficient unloader of PCNA. Unloading requires ATP hydrolysis. This seven-subunit Ctf18-RFC complex consists of the four small subunits of RFC, together with Ctf18, Dcc1, and Ctf8. Ctf18-RFC was also a weak loader of PCNA onto naked template-primer DNA. However, when the single-stranded DNA template was coated by the yeast single-stranded DNA binding protein replication protein A (RPA) but not by a mutant form of RPA or a heterologous single-stranded DNA binding protein, both binding of Ctf18-RFC to substrate DNA and loading of PCNA were strongly inhibited, and unloading predominated. Neither yeast RFC itself nor two other related clamp loaders, containing either Rad24 or Elg1, catalyzed significant unloading of PCNA. The Dcc1 and Ctf8 subunits of Ctf18-RFC, while required for establishing sister chromatid cohesion in vivo, did not function specifically in PCNA unloading in vitro, thereby separating the functionality of the Ctf18-RFC complex into two distinct paths.

scholarly journals Replisome progression complex links DNA replication to sister chromatid cohesion inXenopusegg extracts

2009 ◽  
Vol 14 (8) ◽  
pp. 949-963 ◽  
Author(s):  
Hiroshi Tanaka ◽  
Yumiko Kubota ◽  
Tsuyoshi Tsujimura ◽  
Maya Kumano ◽  
Hisao Masai ◽  
...  
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion

scholarly journals Functional Coupling between DNA Replication and Sister Chromatid Cohesion Establishment

2021 ◽  
Vol 22 (6) ◽  
pp. 2810
Author(s):  
Ana Boavida ◽  
Diana Santos ◽  
Mohammad Mahtab ◽  
Francesca M. Pisani
Keyword(s):  
Dna Replication ◽  
Sister Chromatid ◽  
Molecular Mechanisms ◽  
Sister Chromatid Cohesion ◽  
Functional Coupling ◽  
Functional Link ◽  
Chromatid Cohesion ◽  
Evolutionarily Conserved ◽  
Eukaryotic Organisms ◽  
Replication Factors

Several lines of evidence suggest the existence in the eukaryotic cells of a tight, yet largely unexplored, connection between DNA replication and sister chromatid cohesion. Tethering of newly duplicated chromatids is mediated by cohesin, an evolutionarily conserved hetero-tetrameric protein complex that has a ring-like structure and is believed to encircle DNA. Cohesin is loaded onto chromatin in telophase/G1 and converted into a cohesive state during the subsequent S phase, a process known as cohesion establishment. Many studies have revealed that down-regulation of a number of DNA replication factors gives rise to chromosomal cohesion defects, suggesting that they play critical roles in cohesion establishment. Conversely, loss of cohesin subunits (and/or regulators) has been found to alter DNA replication fork dynamics. A critical step of the cohesion establishment process consists in cohesin acetylation, a modification accomplished by dedicated acetyltransferases that operate at the replication forks. Defects in cohesion establishment give rise to chromosome mis-segregation and aneuploidy, phenotypes frequently observed in pre-cancerous and cancerous cells. Herein, we will review our present knowledge of the molecular mechanisms underlying the functional link between DNA replication and cohesion establishment, a phenomenon that is unique to the eukaryotic organisms.

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