Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic division

Copsey, Alice, Tang, Shangming, Jordan, Philip W, Blitzblau, Hannah, Newcombe, Sonya, Chan, Andrew Chi-ho, Newnham, Louise, Li, Zhaobo, Gray, Steve, Herbert, Alex, Arumugam, Prakash, Hochwagen, Andreas, Hunter, Neil and Hoffmann, Eva (2013) Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic division. PLoS Genetics, 9 (12). e1004071. ISSN 1553-7390

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During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastrophe.

Item Type: Article
Additional Information: PWJ was funded by BBSRC grant (BB/G00353X/1). SG was supported by a MRC Centenary Award. EH is an EMBO Young Investigator and MRC Senior Non-clinical Research Fellow.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Jill Kirby
Date Deposited: 02 Jul 2014 07:36
Last Modified: 02 Jul 2019 20:09

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