Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway (  ). HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (, ). Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) . Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA ( , ). Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (, ). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity). Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging .
Subcellular locations: Nucleus, Chromosome
Associates with sites of DNA damage in S/G2 phase (, ). Ubiquitinated RBBP8 binds to chromatin following DNA damage .
Expressed in ER-positive breast cancer lines, but tends to be down-regulated ER-negative cells (at protein level).