Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse

Brie�o-Enr�quez, Miguel A.; Moak, Stefannie L.; Toledo, Melissa; Filter, Joshua�J.; Gray, Stephen; Barbero, Jos�L.; Cohen, Paula�E.; Holloway, J.�Kim

Abstract

© 2016 The Author(s) Mammalian NIMA-like kinase-1 (NEK1) is a dual-specificity kinase highly expressed in mouse germ cells during prophase I of meiosis. Loss of NEK1 induces retention of cohesin on chromosomes at meiotic prophase I. Timely deposition and removal of cohesin is essential for accurate chromosome segregation. Two processes regulate cohesin removal: a non-proteolytic mechanism involving WAPL, sororin, and PDS5B and direct cleavage by separase. Here, we demonstrate a role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B. This regulation of WAPL by NEK1-PDS5B is mediated by protein phosphatase 1 gamma (PP1γ), which both interacts with and is a phosphotarget of NEK1. Taken together, our results reveal that NEK1 phosphorylates PP1γ, leading to the dephosphorylation of WAPL, which, in turn, resultsinits retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals.

Citation

Brieño-Enríquez, M. A., Moak, S. L., Toledo, M., Filter, J., Gray, S., Barbero, J., Cohen, P., & Holloway, J. (2016). Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse. Cell Reports, 17(4), 977-986. https://doi.org/10.1016/j.celrep.2016.09.059

• Journal Article Type: Article
• Acceptance Date: Sep 16, 2016
• Publication Date: Oct 18, 2016
• Deposit Date: Nov 11, 2019
• Publicly Available Date: Jan 20, 2020
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Electronic ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 4
• Pages: 977-986
• DOI: https://doi.org/10.1016/j.celrep.2016.09.059
• Keywords: General Biochemistry, Genetics and Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/3204128
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2211124716313158
• Additional Information: This article is maintained by: Elsevier; Article Title: Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse; Journal Title: Cell Reports; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.celrep.2016.09.059; Content Type: article; Copyright: © 2016 The Author(s).