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A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes

Lookup NU author(s): Chris Thomas, Ben WetherallORCiD, Dr Mark LevasseurORCiD, Rebecca Harris, Scott Kerridge, Professor Jonathan HigginsORCiD, Dr Owen Davies, Dr Suzanne MadgwickORCiD

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Abstract

Successful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase. Here we find that in meiosis I, mouse oocytes contain an excess of securin over separase. We reveal a mechanism that promotes excess securin destruction in prometaphase I. Importantly, this mechanism relies on two phenylalanine residues within the separase-interacting segment (SIS) of securin that are only exposed when securin is not bound to separase. We suggest that these residues facilitate the removal of non-separase-bound securin ahead of metaphase, as inhibiting this period of destruction by mutating both residues causes the majority of oocytes to arrest in meiosis I. We further propose that cellular securin levels exceed the amount an oocyte is capable of removing in metaphase alone, such that the prometaphase destruction mechanism identified here is essential for correct meiotic progression in mouse oocytes.

Publication metadata

Author(s): Thomas C, Wetherall B, Levasseur MD, Harris RJ, Kerridge ST, Higgins JMG, Davies OR, Madgwick S

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Print publication date: 14/07/2021

Online publication date: 14/07/2021

Acceptance date: 24/06/2021

Date deposited: 27/07/2021

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-021-24554-2

DOI: 10.1038/s41467-021-24554-2

PubMed id: 34262048

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