RT Journal
A1 Mihola, Ondrej
A1 Pratto, Florencia
A1 Brick, Kevin
A1 Linhartova, Eliska
A1 Kobets, Tatyana
A1 Flachs, Petr
A1 Baker, Christopher L.
A1 Sedlacek, Radislav
A1 Paigen, Kenneth
A1 Petkov, Petko M.
A1 Camerini-Otero, R. Daniel
A1 Trachtulec, Zdenek
T1 Histone methyltransferase PRDM9 is not essential for meiosis in male mice
JF Genome Research 
JO Genome Research 
YR 2019 
FD July 01 
VO 29 
IS 7 
SP 1078 
OP 1086 
DO 10.1101/gr.244426.118 
UL http://genome.cshlp.org/content/29/7/1078.abstract 
AB A hallmark of meiosis is the rearrangement of parental alleles to ensure genetic diversity in the gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSBs occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein. Without PRDM9, meiotic DSBs occur near gene promoters and other functional sites. Studies in a limited number of mouse strains showed that functional PRDM9 is required to complete meiosis, but despite its apparent importance, Prdm9 has been repeatedly lost across many animal lineages. Both the reason for mouse sterility in the absence of PRDM9 and the mechanism by which Prdm9 can be lost remain unclear. Here, we explore whether mice can tolerate the loss of Prdm9. By generating Prdm9 functional knockouts in an array of genetic backgrounds, we observe a wide range of fertility phenotypes and ultimately demonstrate that PRDM9 is not required for completion of male meiosis. Although DSBs still form at a common subset of functional sites in all mice lacking PRDM9, meiotic outcomes differ substantially. We speculate that DSBs at functional sites are difficult to repair as a crossover and that by increasing the efficiency of crossover formation at these sites, genetic modifiers of recombination rates can allow for meiotic progression. This model implies that species with a sufficiently high recombination rate may lose Prdm9 yet remain fertile.