Loss of sister kinetochore co-orientation and peri-centromeric cohesin protection after meiosis I depends on cleavage of centromeric REC8.

Jonathan Godwin,Sugako Ogushi,Jean Metson,Lothar Schermelleh,Ahmed Rattani,Kim Nasmyth

doi:10.1016/j.devcel.2021.10.017

Jonathan Godwin, Sugako Ogushi + Show 4 more

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https://doi.org/10.1016/j.devcel.2021.10.017

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Journal: Developmental cell	Publication Date: Nov 1, 2021
Citations: 17	License type: cc-by

Affiliation: University of Oxford, Kyoto University

Abstract

SummaryProtection of peri-centromeric (periCEN) REC8 cohesin from Separase and sister kinetochore (KT) attachment to microtubules emanating from the same spindle pole (co-orientation) ensures that sister chromatids remain associated after meiosis I. Both features are lost during meiosis II, resulting in sister chromatid disjunction and the production of haploid gametes. By transferring spindle-chromosome complexes (SCCs) between meiosis I and II in mouse oocytes, we discovered that both sister KT co-orientation and periCEN cohesin protection depend on the SCC, and not the cytoplasm. Moreover, the catalytic activity of Separase at meiosis I is necessary not only for converting KTs from a co- to a bi-oriented state but also for deprotection of periCEN cohesion, and cleavage of REC8 may be the key event. Crucially, selective cleavage of REC8 in the vicinity of KTs is sufficient to destroy co-orientation in univalent chromosomes, albeit not in bivalents where resolution of chiasmata may also be required

Highlights

Production during meiosis of haploid gametes from diploid germ cells is only possible because two rounds of chromosome segregation occur without an intervening round of DNA replication
Unlike periCEN cohesin, which survives until metaphase II (MII), the protection of CEN cohesin only lasts until late telophase I (TI), whereupon REC8 cleavage induces sister KTs to split into their component parts, setting the scene for their subsequent biorientation during MII. Dyads retain their MII character when transferred to metaphase I (MI) oocytes To address whether factors associated with the spindle-chromosome complex (SCC) or those within the cytoplasm confer coorientation and/or periCEN cohesion protection, we used microsurgery to transfer spindle-chromosome complexes (SCCs) between oocytes
We first addressed how dyads isolated from MII oocytes behave when placed inside MI oocytes

Summary

Introduction

Production during meiosis of haploid gametes from diploid germ cells is only possible because two rounds of chromosome segregation occur without an intervening round of DNA replication. The first division is triggered by cleavage of meiotic cohesin’s REC8 along chromosome arms by a thiol protease ESPL1 called Separase, which resolves chiasmata and creates dyads (Kudo et al, 2006). Two chromatids of these dyads are held together through cohesion between their peri-centromeres, and sister KTs are pulled in opposite directions (bi-orientation) until Separase cleaves remaining cohesin molecules during the second meiotic division. Two key features distinguish the first meiotic division from the second and from mitosis, namely, co-orientation of sister KTs and protection of peri-centromeric (periCEN)

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