Extensive sex differences at the initiation of genetic recombination.
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ABSTRACT:
SUBMITTER: Brick K
PROVIDER: S-EPMC6364566 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Extensive sex differences at the initiation of genetic recombination.
Brick Kevin K Thibault-Sennett Sarah S Smagulova Fatima F Lam Kwan-Wood G KG Pu Yongmei Y Pratto Florencia F Camerini-Otero R Daniel RD Petukhova Galina V GV
Nature 20180905 7723
Meiotic recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at the initiation of recombination by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to fifteen-fold differences in hotspot usage between males and fem ...[more]
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Project description:Meiotic recombination differs between males and females, however, when and how these differences are established is unknown. We identify extensive sex differences at recombination initiation by mapping hotspots of meiotic DNA double strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to 15-fold differences in hotspot use between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex biased hotspots appear to be partly determined by chromosome structure, and DNA methylation, absent in females at the onset of meiosis, plays a substantial role. Sex differences are also evident later in meiosis as the repair frequency of distal meiotic breaks as crossovers diverges in males and females. Suppression of distal crossovers may help to minimize age-related aneuploidy that arises due to cohesion loss during dictyate arrest in females.
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Project description:Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a critical component of complexes of DSB-promoting proteins which assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution owing to reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects are accompanied by a genome-wide delay in assembling DSB-promoting proteins on axes and a loss of a pecialized PAR-axis domain that is highly enriched for DSB-promoting proteins. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated complexes of DSB-promoting proteins.
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Project description:This SuperSeries is composed of the SubSeries listed below.
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