DNA polymerase Β is critical for mouse meiotic synapsis

We have shown earlier that DNA polymerase Β (Pol Β) localizes to the synaptonemal complex (SC) during Prophase I of meiosis in mice. Pol Β localizes to synapsed axes during zygonema and pachynema, and it associates with the ends of bivalents during late pachynema and diplonema. To test whether these localization patterns reflect a function for Pol Β in recombination and/or synapsis, we used conditional gene targeting to delete the PolB gene from germ cells. We find that Pol Β-deficient spermatocytes are defective in meiotic chromosome synapsis and undergo apoptosis during Prophase I. We also find that SPO11-dependent γH2AX persists on meiotic chromatin, indicating that Pol Β is critical for the repair of SPO11-induced double-strand breaks (DSBs). Pol Β-deficient spermatocytes yielded reduced steady-state levels of the SPO11-oligonucleotide complexes that are formed when SPO11 is removed from the ends of DSBs, and cytological experiments revealed that chromosome-associated foci of replication protein A (RPA), RAD51 and DMC1 are less abundant in Pol Β-deficient spermatocyte nuclei. Localization of Pol Β to meiotic chromosomes requires the formation of SPO11-dependent DSBs. Taken together, these findings strongly indicate that Pol Β is required at a very early step in the processing of meiotic DSBs, at or before the removal of SPO11 from DSB ends and the generation of the 3′ single-stranded tails necessary for subsequent strand exchange. The chromosome synapsis defects and Prophase I apoptosis of Pol Β-deficient spermatocytes are likely a direct consequence of these recombination defects.