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Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome
Patients with Cornelia de Lange Syndrome (CdLS) often have mutations in cohesin and its regulators; however, the molecular mechanism driving CdLS phenotypes is not well established. Here the authors reveal system skeletal organization genes are downregulated and show that cohesin and its loader Nipbl have altered and decreased genome-wide localization.
- Patricia Garcia
- , Rita Fernandez-Hernandez
- & Ethel Queralt
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Article
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A requirement for STAG2 in replication fork progression creates a targetable synthetic lethality in cohesin-mutant cancers
Cohesin complex mediates cohesion of sister chromatids and DNA loop formation. Here the authors show another role of cohesin in replication fork progression, suggesting a potential therapeutic strategy for cohesin-mutant cancers.
- Gourish Mondal
- , Meredith Stevers
- & David A. Solomon
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Article
| Open Access
The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation
The chromatin remodeler RSF1 is enriched at mitotic centromeres but its function there is poorly understood. Here, the authors show that RSF1 regulates H2A phosphorylation and acetylation at mitotic centromeres and contributes to chromosome stability.
- Ho-Soo Lee
- , Zhonghui Lin
- & Hyeseong Cho
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Article
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Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I
In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.
- Warif El Yakoubi
- , Eulalie Buffin
- & Katja Wassmann
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Article
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Inner centromere localization of the CPC maintains centromere cohesion and allows mitotic checkpoint silencing
Precise chromosome segregation during mitosis requires coordination of stable chromosome bi-orientation with anaphase onset, however the underlying mechanism is not clear. Here the authors show that inner centromere localization of the chromosomal passenger complex maintains centromeric cohesion on bi-oriented chromosomes and allows mitotic checkpoint silencing.
- Rutger C. C. Hengeveld
- , Martijn J. M. Vromans
- & Susanne M. A. Lens
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Article
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Topology and structure of an engineered human cohesin complex bound to Pds5B
Cohesin is a ring-shaped protein complex that structures chromatin and mediates sister chromatid cohesion. Here the authors rigidify cohesin using engineered Smc1 and Smc3 and generated 3D models showing how Pds5B forms an integral part of the cohesin ring.
- Michael T. Hons
- , Pim J. Huis in ‘t Veld
- & Jan-Michael Peters
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Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function
Cohesion is associated with many forms of cancer. De Lange et al. show that such cohesion defects can sensitise cells to apoptosis in response to a new APC/C ubiquitin ligase inhibitor, by prolonging mitotic arrest and checkpoint activation due to cohesion fatigue.
- Job de Lange
- , Atiq Faramarz
- & Rob M. F. Wolthuis
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Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion
The Ssu72 phosphatase is required to prevent premature separation of sister chromatids during interphase. Kim et al.show that this signal is terminated at early mitosis by Aurora B, which phosphorylates Ssu72 and promotes its ubiquitin-dependent degradation.
- Hyun-Soo Kim
- , Se-Hyuk Kim
- & Chang-Woo Lee
Functional crosstalk between the cohesin loader and chromatin remodelers