RBBP8 Protein, Human (His, Strep)

RBBP8 is an 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 the S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. RBBP8 is a key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). It specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts: recruited to DSBs by NBN following phosphorylation by CDK1, and promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends. It functions downstream of the MRN complex and ATM, promoting ATR activation and its recruitment to DSBs in the S/G2 phase, facilitating the generation of ssDNA. As a component of the BRCA1-RBBP8 complex, it regulates CHEK1 activation and controls cell cycle G2/M checkpoints upon DNA damage. During immunoglobulin heavy chain class-switch recombination, it promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (by similar). It binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging.