AtMCM10 facilitates SDSA-mediated intermolecular homologous recombination repair via liquid-liquid phase separation in DNA damage response.

Mini-Chromosome Maintenance 10 (MCM10) is essential for maintaining genome stability by facilitating DNA replication and repair across various organisms. While the role of MCM10 in DNA replication is well-established, its mechanism in DNA repair remains less understood. In this study, we demonstrate that loss of AtMCM10 function leads to increased DNA damage under genotoxic or salinity stress in Arabidopsis thaliana. Detailed analysis reveals that AtMCM10 works primarily downstream of ATM and is crucial for intermolecular homologous recombination (HR) mediated by synthesis-dependent strand annealing (SDSA) in response to DNA damage. Further cytological and biochemical analyses reveal that AtMCM10 possesses DNA annealing activity, colocalizes with the double-strand break (DSB) sites, and undergoes liquid-liquid phase separation (LLPS) upon DNA damage, facilitated by single strand DNA (ssDNA) in vitro. Altogether, our findings indicate that AtMCM10 acts as a single-strand DNA (ssDNA) annealing protein to promote SDSA-mediated intermolecular HR repair via LLPS in somatic cells upon DNA damage, providing new insights into the HR repair mechanisms.