Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes

Abstract

During female meiosis, bivalent chromosomes are thought to be held together from birth until ovulation by sister chromatid cohesion mediated by cohesin complexes whose ring structure depends on kleisin subunits, either Rec8 or Scc1. Because cohesion is established at DNA replication in the embryo, its maintenance for such a long time may require cohesin turnover. To address whether Rec8-or Scc1-containing cohesin holds bivalents together and whether it turns over, we created mice whose kleisin subunits can be cleaved by TEV protease. We show by microinjection experiments and confocal live-cell imaging that Rec8 cleavage triggers chiasmata resolution during meiosis I and sister centromere disjunction during meiosis II, while Scc1 cleavage triggers sister chromatid disjunction in the first embryonic mitosis, demonstrating a dramatic transition from Rec8-to Scc1-containing cohesin at fertilization. Crucially, activation of an ectopic Rec8 transgene during the growing phase of Rec8 TEV/TEV oocytes does not prevent TEV-mediated bivalent destruction, implying little or no cohesin turnover for $2 wk during oocyte growth. We suggest that the inability of oocytes to regenerate cohesion may contribute to agerelated meiosis I errors.[Keywords: Cohesin; Rec8; meiosis; oocytes] Supplemental material is available at http://www.genesdev.org.

The association between the oocyte pool and aneuploidy: a comparative study of the reproductive potential of young and aged mice

“…It is reported that the expression of oocyte genes that are related to cell cycle regulation, cytoskeleton structure, metabolic pathways, transcription control, and stress responses, were influenced by maternal age [43]. In this study, no difference in the relative expression levels of the SMC3, SMC1β and STAG3 mRNAs between the groups was observed, and no REC8 mRNA expression was found (Supplementary Data Figure 1), most likely because little or no Cohesin turnover occurs for over 2 weeks during oocyte growth [44].…”

Genetic Evidence That Synaptonemal Complex Axial Elements Govern Recombination Pathway Choice in Mice

“…Additionally, in most organisms, crossing over is essential to ensure accurate segregation of homologous chromosome pairs at the first meiotic division. Cohesin-stabilized chiasmata physically tether homologous chromosomes, contributing to their eventual congression to, and coalignment at the metaphase plate (Hodges et al 2005;Tachibana-Konwalski et al 2010). There, the pair is held in balance by opposing forces: centromere cohesion and chiasmata maintaining attachment on one hand vs. spindle fibers pulling each homolog toward opposite poles.…”

Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes

“…A lack of turnover of the meiotic cohesin protein is considered to contribute to age-related chromosome segregation errors in oocytes. [32][33][34] The molecular mechanisms that maintain or disrupt meiotic cohesion have remained unclear for many decades. However, the candidate genes in cluster 2 in our current study may assist with our understanding of this complex phenomenon going forward.…”