AbstractIn many mammals, genomic sites for recombination are determined by histone methyltransferase PRMD9. Mice lacking PRDM9 are infertile, but instances of fertility or semi-fertility in the absence of PRDM9 have been reported in mice, canines and a human female. Such findings raise the question of how the loss of PRDM9 is circumvented to maintain reproductive fitness. We show that genetic background and sex-specific modifiers can obviate the requirement for PRDM9 in mice. Specifically, the meiotic DNA damage checkpoint protein CHK2 acts as a modifier allowing female-specific fertility in the absence of PRDM9. We also report that in the absence of PRDM9, a PRDM9-independent recombination system is compatible with female meiosis and fertility, suggesting sex-specific regulation of meiotic recombination, a finding with implications for speciation.One Sentence SummarySex-specific modulation of a meiotic DNA damage checkpoint limits the requirement for PRDM9 in mammalian fertility.
The DNA damage checkpoint protein RAD9A is essential for male meiosis in the mouse
