Distinct Properties of the XY Pseudoautosomal Region Crucial for Male Meiosis

被引:193
作者
Kauppi, Liisa [1 ]
Barchi, Marco [2 ,3 ]
Baudat, Frederic [2 ]
Romanienko, Peter J. [2 ]
Keeney, Scott [1 ,4 ]
Jasin, Maria [2 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA
[2] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA
[3] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Sect Anat, I-00133 Rome, Italy
[4] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA
关键词
DOUBLE-STRAND BREAKS; CHROMOSOME SYNAPSIS; MOUSE; RECOMBINATION; SPO11; SPERMATOCYTES; MICE; PROTEINS; PROPHASE; OOCYTES;
D O I
10.1126/science.1195774
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:916 / 920
页数:5
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