부산대학교 도서관

The BRCA2 tumor suppressor is a DNA double‐strand break (DSB) repair factor essential for maintaining genome integrity. BRCA2‐deficient cells spontaneously accumulate DNA‐RNA hybrids, a known source of genome instability. However, the specific role of BRCA2 on these structures remains poorly understood. Here we identified the DEAD‐box RNA helicase DDX5 as a BRCA2‐interacting protein. DDX5 associates with DNA‐RNA hybrids that form in the vicinity of DSBs, and this association is enhanced by BRCA2. Notably, BRCA2 stimulates the DNA‐RNA hybrid‐unwinding activity of DDX5 helicase. An impaired BRCA2‐DDX5 interaction, as observed in cells expressing the breast cancer variant BRCA2‐T207A, reduces the association of DDX5 with DNA‐RNA hybrids, decreases the number of RPA foci, and alters the kinetics of appearance of RAD51 foci upon irradiation. Our findings are consistent with DNA‐RNA hybrids constituting an impediment for the repair of DSBs by homologous recombination and reveal BRCA2 and DDX5 as active players in their removal. SYNOPSIS: Cells lacking the BRCA2 tumor suppressor spontaneously accumulate DNA‐RNA hybrids, but the specific BRCA2 role in their suppression has remained unclear. Here, RNA helicase DDX5 is found to interact with BRCA2 and participate in R‐loop ressolution to allow homologous recombination (HR) repair. BRCA2 and DDX5 cooperate to unwind DNA double‐strand break‐associated R‐loops at transcribed regions.BRCA2 supports DDX5 association with DNA double‐strand breaks.Interaction between BRCA2 and DDX5 facilitates timely repair of DNA damage by HR.The breast‐cancer‐associated T207A mutation alters BRCA2 interaction with DDX5 and slows the kinetics of HR repair. [ABSTRACT FROM AUTHOR]