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

Autor: Thomas C; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. christopher.thomas@mpibpc.mpg.de.; Max Planck Institute for Biophysical Chemistry, Gottingen, Germany. christopher.thomas@mpibpc.mpg.de., Wetherall B; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Levasseur MD; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Harris RJ; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Kerridge ST; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Higgins JMG; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Davies OR; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.; Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh, UK., Madgwick S; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. suzanne.madgwick@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jul 14; Vol. 12 (1), pp. 4322. Date of Electronic Publication: 2021 Jul 14.
DOI: 10.1038/s41467-021-24554-2
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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