Abstract
SummarySister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation in mitosis and meiosis [1]. Rec8-containing cohesin, bound to Smc3/Smc1α or Smc3/Smc1β, maintains bivalent cohesion in mammalian meiosis [2, 3, 4, 5, 6]. In females, meiotic DNA replication and recombination occur in fetal oocytes. After birth, oocytes arrest at the prolonged dictyate stage until recruited to grow into mature oocytes that divide at ovulation. How cohesion is maintained in arrested oocytes remains a pivotal question relevant to maternal age-related aneuploidy. Hypothetically, cohesin turnover regenerates cohesion in oocytes. Evidence for post-replicative cohesion establishment mechanism exists, in yeast and invertebrates [7, 8]. In mouse fetal oocytes, cohesin loading factor Nipbl/Scc2 localizes to chromosome axes during recombination [9, 10]. Alternatively, cohesion is maintained without turnover. Consistent with this, cohesion maintenance does not require Smc1β transcription, but unlike Rec8, Smc1β is not required for establishing bivalent cohesion [11, 12]. Rec8 maintains cohesion without turnover during weeks of oocyte growth [3]. Whether the same applies to months or decades of arrest is unknown. Here, we test whether Rec8 activated in arrested mouse oocytes builds cohesion revealed by TEV cleavage and live-cell imaging. Rec8 establishes cohesion when activated during DNA replication in fetal oocytes using tamoxifen-inducible Cre. In contrast, no new cohesion is detected when Rec8 is activated in arrested oocytes by tamoxifen despite cohesin synthesis. We conclude that cohesion established in fetal oocytes is maintained for months without detectable turnover in dictyate-arrested oocytes. This implies that women’s fertility depends on the longevity of cohesin proteins that established cohesion in utero.
Highlights
A Functional Cohesion Rescue Assay in Meiosis I Oocytes The entrapment of sister DNA molecules by cohesin complexes can be measured indirectly and directly using biochemical a
Most aneuploid pregnancies arise as a consequence of chromosome segregation errors during the first meiotic division of female germ cells called oocytes, leading to aneuploid eggs [13,14,15]
Overall our results show that sister chromatid cohesion mediated by Rec8-containing cohesin complexes is established in fetal oocytes and maintained without detectable turnover after birth, both during the prolonged dictyate-stage arrest and the weeks of oocyte growth [3]
Summary
How chromosome cohesion is maintained in female germ cells arrested for months or decades is poorly understood. Burkhardt et al show that cohesion is built in fetal oocytes and after birth is maintained without detectable renewal for months. This implies that the oocyte’s inability to renew cohesion contributes to maternal age-related trisomies.
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