Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I.
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...
| Príomhchruthaitheoirí: | , , , , , , , , |
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| Formáid: | Journal article |
| Teanga: | English |
| Foilsithe / Cruthaithe: |
2009
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| _version_ | 1826263284721909760 |
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| author | Kudo, N Anger, M Peters, A Stemmann, O Theussl, H Helmhart, W Kudo, H Heyting, C Nasmyth, K |
| author_facet | Kudo, N Anger, M Peters, A Stemmann, O Theussl, H Helmhart, W Kudo, H Heyting, C Nasmyth, K |
| author_sort | Kudo, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:49:18Z |
| format | Journal article |
| id | oxford-uuid:236aec36-1712-4482-a04b-7996dce2f954 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:49:18Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:236aec36-1712-4482-a04b-7996dce2f9542022-03-26T11:44:13ZRole of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:236aec36-1712-4482-a04b-7996dce2f954EnglishSymplectic Elements at Oxford2009Kudo, NAnger, MPeters, AStemmann, OTheussl, HHelmhart, WKudo, HHeyting, CNasmyth, KProteolytic 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. |
| spellingShingle | Kudo, N Anger, M Peters, A Stemmann, O Theussl, H Helmhart, W Kudo, H Heyting, C Nasmyth, K Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. |
| title | Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. |
| title_full | Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. |
| title_fullStr | Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. |
| title_full_unstemmed | Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. |
| title_short | Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. |
| title_sort | role of cleavage by separase of the rec8 kleisin subunit of cohesin during mammalian meiosis i |
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