Journal
SCIENCE
Volume 331, Issue 6019, Pages 916-920Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1195774
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Funding
- NIH [R01 HD040916]
- International Grants in Cancer Research (AIRC) [4765]
- Italian Ministry for Education, University and Research (MIUR)
- Lalor Foundation
- American-Italian Cancer Foundation (AICF)
- Charles H. Revson Foundation
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Meiosis requires that each chromosome find its homologous partner and undergo at least one crossover. X-Y chromosome segregation hinges on efficient crossing-over in a very small region of homology, the pseudoautosomal region (PAR). We find that mouse PAR DNA occupies unusually long chromosome axes, potentially as shorter chromatin loops, predicted to promote double-strand break (DSB) formation. Most PARs show delayed appearance of RAD51/DMC1 foci, which mark DSB ends, and all PARs undergo delayed DSB-mediated homologous pairing. Analysis of Spo11 beta isoform-specific transgenic mice revealed that late RAD51/DMC1 foci in the PAR are genetically distinct from both early PAR foci and global foci and that late PAR foci promote efficient X-Y pairing, recombination, and male fertility. Our findings uncover specific mechanisms that surmount the unique challenges of X-Y recombination.
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