Moss BRCA2 lacking canonical DNA binding domain promotes efficient homologous recombination and binds to DNA

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Abstract
BRCA2 interacts with RAD51 and DMC1 recombinases and binds to single-stranded DNA (ssDNA), through its canonical DNA binding domain (DBD) to mediate homology-directed DNA repair (HDR). While the well-folded DBD is widely conserved in diverse eukaryotes, a non-canonical BRCA2 variant lacking this domain is found in Drosophila melanogaster . Whether such a non-canonical BRCA2 variant exists in other species is unknown. Additionally, the DNA-binding activity of a BRCA2 variant lacking DBD remains unclear. Here, we identify a new non-canonical BRCA2 in the model plant Physcomitrium patens (PpBRCA2). We establish that PpBRCA2 is essential for genome integrity maintenance, somatic DNA repair, HDR-mediated gene targeting, and RAD51 foci recruitment at DNA break sites. PpBRCA2 is also critical for DNA repair during meiosis, but interacts only weakly with DMC1, suggesting a distinct meiotic function compared to other BRCA2 homologs. Despite lacking the canonical DBD, PpBRCA2 binds ssDNA through its disordered N-terminal region and efficiently promotes HDR. Our work highlights that the ssDNA binding capacity of BRCA2 homologs is conserved regardless of the presence of canonical DBD and provides a deeper understanding of BRCA2’s functional diversity across species. Three Key messages: Physcomitrium patens BRCA2 (PpBRCA2) lacking canonical DBD mediates homologous recombination and promotes genome stability PpBRCA2 differentially interact with RAD51 and DMC1 PpBRCA2 binds single-stranded DNA via its N-terminal to compensate for the loss of canonical DBD
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