ssDNA dynamics during mammalian meiotic recombination†

Programmed DNA double-strand breaks (DSBs) are a hallmark of meiosis, which have to be precisely repaired through meiotic recombination for ensuring genome stability and ultimately generating haploid gametes. Single-stranded DNA (ssDNA) is a central intermediate during DNA repair, primarily generated by nucleolytic resection of DSB ends and by strand displacement during homology search and strand invasion. In mammalian meiosis, resected 3' ssDNA overhangs are rapidly coated by replication protein A (RPA), which stabilizes ssDNA and prevents secondary structure formation. Subsequently, with the assistance of BRCA2 and other accessory factors, the recombinases RAD51 and DMC1 are loaded onto DSB sites to form nucleoprotein filaments. Furthermore, a meiosis-specific ssDNA-binding complex, the MEIOB/SPATA22 heterodimer, regulates recombination intermediate stability and processing. In addition, ssDNA can hybridize with RNA to form DNA-RNA hybrids, representing another way for ssDNA utilization. In this review, we summarize current knowledge of ssDNA generation, utilization, and turnover during mammalian meiotic recombination and highlight unresolved questions for further investigation.