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Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I

Title data

Kudo, Nobuaki R. ; Anger, Martin ; Peters, Antoine H. ; Stemmann, Olaf ; Theussl, Hans-Christian ; Helmhart, Wolfgang ; Kudo, Hiromi ; Heyting, Christa ; Nasmyth, Kim:
Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I.
In: Journal of Cell Science. Vol. 122 (1 August 2009) . - pp. 2686-2698.
ISSN 1477-9137
DOI: https://doi.org/10.1242/jcs.035287

Official URL: Volltext

Abstract in another language

Proteolytic activity of separase is required for chiasma resolution during meiosis I in mouse oocytes. Rec8, the meiosis-specific alpha-kleisin subunit of cohesin, is a key target of separase in yeast. Is the equivalent protein also a target in mammals? We show here that separase cleaves mouse Rec8 at three positions in vitro but only when the latter is hyper-phosphorylated. Expression of a Rec8 variant (Rec8-N) that cannot be cleaved in vitro at these sites causes sterility in male mice. Their seminiferous tubules lack a normal complement of 2 C secondary spermatocytes and 1 C spermatids and contain instead a high proportion of cells with enlarged nuclei. Chromosome spreads reveal that Rec8-N expression has no effect in primary spermatocytes but produces secondary spermatocytes and spermatids with a 4 C DNA content, suggesting that the first and possibly also the second meiotic division is abolished. Expression of Rec8-N in oocytes causes chromosome segregation to be asynchronous and delays its completion by 2-3 hours during anaphase I, probably due to inefficient proteolysis of Rec8-N by separase. Despite this effect, chromosome segregation must be quite accurate as Rec8-N does not greatly reduce female fertility. Our data is consistent with the notion that Rec8 cleavage is important and probably crucial for the resolution of chiasmata in males and females.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics > Chair Genetics - Univ.-Prof. Dr. Olaf Stemmann
Profile Fields > Advanced Fields > Molecular Biosciences
Research Institutions > Research Centres > Bayreuth Center for Molecular Biosciences - BZMB
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics
Profile Fields
Profile Fields > Advanced Fields
Research Institutions
Research Institutions > Research Centres
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 26 Mar 2015 10:13
Last Modified: 18 Apr 2018 08:53
URI: https://eref.uni-bayreuth.de/id/eprint/8457