Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I.
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Kudo, Nobuaki R, Anger, Martin, Peters, Antoine, Stemmann, Olaf, Theussl, Hans-Christian, Helmhart, Wolfgang, Kudo, Hiromi, Heyting, Christa and Nasmyth, Kim (2009) Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. Journal of Cell Science, 122 (Pt 15). pp. 2686-9268. ISSN 0021-9533
Abstract
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.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); On author's personal web site; Publisher's version/PDF may be used |
| Keywords: | Chromosome segregation; Cohesin; Meiosis; Oocyte maturation; Separase; Spermatogenesis |
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| Date Deposited: | 14 Dec 2009 13:49 |
| Last Modified: | 31 Jan 2013 00:57 |
| URI: | https://oak.novartis.com/id/eprint/1177 |