4.7 Article

Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition

Journal

DEVELOPMENTAL CELL
Volume 56, Issue 15, Pages 2192-+

Publisher

CELL PRESS
DOI: 10.1016/j.devcel.2021.06.019

Keywords

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Funding

  1. Harold G & Leila Y. Mathers Charitable Foundation
  2. NSF [2029868]
  3. Global Consortium for Reproductive Longevity and Equity
  4. NIH/NIGMS [R35GM126930, GM122475]
  5. Henry and Frances Keany Rickard Fund Fellowship from the MIT Office of Graduate Education
  6. Direct For Biological Sciences
  7. Div Of Molecular and Cellular Bioscience [2029868] Funding Source: National Science Foundation

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The protease separase rewires key cell division processes by cleaving the meiosis-specific protein Meikin at the meiosis I/II transition. This cleavage alters the function of Meikin and plays a distinct role in controlling meiosis, ultimately leading to defective chromosome alignment in oocytes. Multiple regulatory events irreversibly modulate Meikin activity during successive meiotic divisions.
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.

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