Moss BRCA2 lacking the canonical DNA-binding domain promotes homologous recombination and binds to DNA
BRCA2 is crucial for mediating homology-directed DNA repair (HDR) through its binding to single-stranded DNA (ssDNA) and the recombinases RAD51 and DMC1. Most BRCA2 orthologs have a canonical DNA-binding domain (DBD) with the exception of Drosophila melanogaster. It remains unclear whether such a noncanonical BRCA2 variant without DBD possesses a DNA-binding activity. Here, we identify a new noncanonical BRCA2 in the model plant Physcomitrium patens (PpBRCA2). We establish that PpBRCA2 is essential for genome integrity maintenance, somatic DNA double-strand break (DSB) repair, HDR-mediated gene targeting, and RAD51 foci recruitment at DNA break sites. PpBRCA2 is also critical for DSB repair during meiosis. Interestingly, PpBRCA2 interacts strongly with RAD51 but 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 a canonical DBD and provides a deeper understanding of BRCA2's functional diversity across species.
Authors
- Simona Miron (ORCID: https://orcid.org/0000-0003-0565-9958)
- P. Dupaigne (ORCID: https://orcid.org/0000-0001-7033-4055)
- Rajeev Kumar (ORCID: https://orcid.org/0000-0002-3895-8164)
- Fabien Nogué (ORCID: https://orcid.org/0000-0003-0619-4638)
- Sophie Zinn‐Justin (ORCID: https://orcid.org/0000-0002-7680-1088)
- Pierre‐François Perroud (ORCID: https://orcid.org/0000-0001-7607-3618)
- Sreejith Allipra (ORCID: https://orcid.org/0000-0002-2394-8342)
- Alice Chanteau (ORCID: https://orcid.org/0009-0009-1463-1843)
- Suliane Quilleré (ORCID: https://orcid.org/0009-0002-3739-2581)
- Arthur Crouset
- Ulysse Tuquoi (ORCID: https://orcid.org/0009-0003-3837-2635)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut de Biologie Intégrative de la Cellule (FR)
- Institut Jean-Pierre Bourgin (FR)
- CEA Paris-Saclay (FR)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-08-15
- DOI
- https://doi.org/10.1093/nar/gkaf856
- Citations
- 1
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- French Infrastructure for Integrated Structural Biology