scholarly journals S-Phase Checkpoint Genes Safeguard High-Fidelity Sister Chromatid Cohesion

2004 ◽  
Vol 15 (4) ◽  
pp. 1724-1735 ◽  
Author(s):  
Cheryl D. Warren ◽  
D. Mark Eckley ◽  
Marina S. Lee ◽  
Joseph S. Hanna ◽  
Adam Hughes ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Synthetic Lethal ◽  
Specific Subset ◽  
Chromatid Cohesion ◽  
Dna Replication And Repair ◽  
Checkpoint Genes ◽  
Additional Role ◽  
S Phase Checkpoint

Cohesion establishment and maintenance are carried out by proteins that modify the activity of Cohesin, an essential complex that holds sister chromatids together. Constituents of the replication fork, such as the DNA polymerase α-binding protein Ctf4, contribute to cohesion in ways that are poorly understood. To identify additional cohesion components, we analyzed a ctf4Δ synthetic lethal screen performed on microarrays. We focused on a subset of ctf4Δ-interacting genes with genetic instability of their own. Our analyses revealed that 17 previously studied genes are also necessary for the maintenance of robust association of sisters in metaphase. Among these were subunits of the MRX complex, which forms a molecular structure similar to Cohesin. Further investigation indicated that the MRX complex did not contribute to metaphase cohesion independent of Cohesin, although an additional role may be contributed by XRS2. In general, results from the screen indicated a sister chromatid cohesion role for a specific subset of genes that function in DNA replication and repair. This subset is particularly enriched for genes that support the S-phase checkpoint. We suggest that these genes promote and protect a chromatin environment conducive to robust 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 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 Hardwired synthetic lethality within the cohesin complex in human cancer cells

2017 ◽  
Author(s):  
Petra van der Lelij ◽  
Simone Lieb ◽  
Julian Jude ◽  
Gordana Wutz ◽  
Catarina P. Santos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Cohesin Complex ◽  
Wild Type ◽  
Synthetic Lethal ◽  
Recurrent Mutations ◽  
Wide Range ◽  
Chromatid Cohesion

AbstractRecent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 act redundantly to support sister chromatid cohesion and cell survival. STAG1 represents a hardwired, context independent vulnerability of cancer cells carrying mutations in the major emerging tumor suppressor STAG2. Exploiting synthetic lethal interactions to target recurrent cohesin mutations in cancer, e.g. by inhibiting STAG1, holds the promise for the development of selective therapeutics.

scholarly journals Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts

2017 ◽  
Author(s):  
Petra van der Lelij ◽  
Simone Lieb ◽  
Julian Jude ◽  
Gordana Wutz ◽  
Catarina P. Santos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Sister Chromatid ◽  
Synthetic Lethality ◽  
Sister Chromatid Cohesion ◽  
Cohesin Complex ◽  
Wild Type ◽  
Synthetic Lethal ◽  
Recurrent Mutations ◽  
Wide Range ◽  
Chromatid Cohesion

AbstractRecent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 support sister chromatid cohesion to redundantly ensure cell survival. STAG1 represents a vulnerability of cancer cells carrying mutations in the major emerging tumor suppressor STAG2 across different cancer contexts. Exploiting synthetic lethal interactions to target recurrent cohesin mutations in cancer, e.g. by inhibiting STAG1, holds the promise for the development of selective therapeutics.

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):  
Fission Yeast ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion

scholarly journals ATP dependent DNA transport within cohesin: Scc2 clamps DNA on top of engaged heads while Scc3 promotes entrapment within the SMC-kleisin ring

2020 ◽  
Author(s):  
James E Collier ◽  
Byung-Gil Lee ◽  
Maurici B Roig ◽  
Stanislav Yatskevich ◽  
Naomi J Petela ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Atp Hydrolysis ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Coiled Coils ◽  
Rigorous Proof ◽  
Dna Loops ◽  
Dna Transport ◽  
Chromatid Cohesion

SUMMARYIn addition to extruding DNA loops, cohesin entraps within its SMC-kleisin ring (S-K) individual DNAs during G1 and sister DNAs during S-phase. All three activities require related hook-shaped proteins called Scc2 and Scc3. Using thiol-specific crosslinking we provide rigorous proof of entrapment activity in vitro. Scc2 alone promotes entrapment of DNAs in the E-S and E-K compartments, between ATP-bound engaged heads and the SMC hinge and associated kleisin, respectively. This does not require ATP hydrolysis nor is it accompanied by entrapment within S-K rings, which is a slower process requiring Scc3. Cryo-EM reveals that DNAs transported into E-S/E-K compartments are “clamped” in a sub-compartment created by Scc2’s association with engaged heads whose coiled coils are folded around their elbow. We suggest that clamping may be a recurrent feature of cohesin complexes active in loop extrusion and that this conformation precedes the S-K entrapment required for sister chromatid cohesion.

scholarly journals Acetylation of Smc3 by Eco1 Is Required for S Phase Sister Chromatid Cohesion in Both Human and Yeast

2008 ◽  
Vol 31 (1) ◽  
pp. 143-151 ◽  
Author(s):  
Jinglan Zhang ◽  
Xiaomin Shi ◽  
Yehua Li ◽  
Beom-Jun Kim ◽  
Junling Jia ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion
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