Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition
To generate haploid gametes, germ cells undergo two consecutive meiotic divisions requiring key changes to the cell division machinery. Here, we demonstrate that the protease separase rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin....
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/146777 |
| _version_ | 1811080331213668352 |
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| author | Maier, Nolan K Ma, Jun Lampson, Michael A Cheeseman, Iain M |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Maier, Nolan K Ma, Jun Lampson, Michael A Cheeseman, Iain M |
| author_sort | Maier, Nolan K |
| collection | MIT |
| description | To generate haploid gametes, germ cells undergo two consecutive meiotic divisions requiring key changes to the cell division machinery. Here, we demonstrate that the protease separase rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin. Separase proteolysis does not inactivate Meikin but instead alters its function to create a distinct activity state. Full-length Meikin and the C-terminal Meikin separase cleavage product both localize to kinetochores, bind to Plk1 kinase, and promote Rec8 cleavage, but our results reveal distinct roles for these proteins in controlling meiosis. Mutations that prevent Meikin cleavage or that conditionally inactivate Meikin at anaphase I result in defective meiosis II chromosome alignment in mouse oocytes. Finally, as oocytes exit meiosis, C-Meikin is eliminated by APC/C-mediated degradation prior to the first mitotic division. Thus, multiple regulatory events irreversibly modulate Meikin activity during successive meiotic divisions to rewire the cell division machinery at two distinct transitions. |
| first_indexed | 2024-09-23T11:29:32Z |
| format | Article |
| id | mit-1721.1/146777 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:29:32Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1467772022-12-08T03:28:49Z Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition Maier, Nolan K Ma, Jun Lampson, Michael A Cheeseman, Iain M Massachusetts Institute of Technology. Department of Biology To generate haploid gametes, germ cells undergo two consecutive meiotic divisions requiring key changes to the cell division machinery. Here, we demonstrate that the protease separase rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin. Separase proteolysis does not inactivate Meikin but instead alters its function to create a distinct activity state. Full-length Meikin and the C-terminal Meikin separase cleavage product both localize to kinetochores, bind to Plk1 kinase, and promote Rec8 cleavage, but our results reveal distinct roles for these proteins in controlling meiosis. Mutations that prevent Meikin cleavage or that conditionally inactivate Meikin at anaphase I result in defective meiosis II chromosome alignment in mouse oocytes. Finally, as oocytes exit meiosis, C-Meikin is eliminated by APC/C-mediated degradation prior to the first mitotic division. Thus, multiple regulatory events irreversibly modulate Meikin activity during successive meiotic divisions to rewire the cell division machinery at two distinct transitions. 2022-12-07T16:05:31Z 2022-12-07T16:05:31Z 2021 2022-12-07T15:26:50Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146777 Maier, Nolan K, Ma, Jun, Lampson, Michael A and Cheeseman, Iain M. 2021. "Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition." Developmental Cell, 56 (15). en 10.1016/J.DEVCEL.2021.06.019 Developmental Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Maier, Nolan K Ma, Jun Lampson, Michael A Cheeseman, Iain M Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition |
| title | Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition |
| title_full | Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition |
| title_fullStr | Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition |
| title_full_unstemmed | Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition |
| title_short | Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition |
| title_sort | separase cleaves the kinetochore protein meikin at the meiosis i ii transition |
| url | https://hdl.handle.net/1721.1/146777 |
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