Emerging themes in cohesin cancer biology
- 1 September 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Cancer
- Vol. 20 (9), 504-515
- https://doi.org/10.1038/s41568-020-0270-1
Abstract
Mutations of the cohesin complex in human cancer were first discovered similar to 10 years ago. Since then, researchers worldwide have demonstrated that cohesin is among the most commonly mutated protein complexes in cancer. Inactivating mutations in genes encoding cohesin subunits are common in bladder cancers, paediatric sarcomas, leukaemias, brain tumours and other cancer types. Also in those 10 years, the prevailing view of the functions of cohesin in cell biology has undergone a revolutionary transformation. Initially, the predominant view of cohesin was as a ring that encircled and cohered replicated chromosomes until its cleavage triggered the metaphase-to-anaphase transition. As such, early studies focused on the role of tumour-derived cohesin mutations in the fidelity of chromosome segregation and aneuploidy. However, over the past 5 years the cohesin field has shifted dramatically, and research now focuses on the primary role of cohesin in generating, maintaining and regulating the intra-chromosomal DNA looping events that modulate 3D genome organization and gene expression. This Review focuses on recent discoveries in the cohesin field that provide insight into the role of cohesin inactivation in cancer pathogenesis, and opportunities for exploiting these findings for the clinical benefit of patients with cohesin-mutant cancers.This publication has 129 references indexed in Scilit:
- Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancyNature Genetics, 2013
- Integrated genomic characterization of endometrial carcinomaNature, 2013
- Clonal diversity of recurrently mutated genes in myelodysplastic syndromesLeukemia, 2013
- The Origin and Evolution of Mutations in Acute Myeloid LeukemiaCell, 2012
- RAD21 Mutations Cause a Human CohesinopathyAmerican Journal of Human Genetics, 2012
- Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeresThe EMBO Journal, 2012
- Evidence that Weakened Centromere Cohesion Is a Leading Cause of Age-Related Aneuploidy in OocytesCurrent Biology, 2010
- Mediator and cohesin connect gene expression and chromatin architectureNature, 2010
- Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center originNature Genetics, 2010
- Cohesin acetylation speeds the replication forkNature, 2009