RBBP8
Description
The RBBP8 (RB binding protein 8, endonuclease) is a protein-coding gene located on chromosome 18.
Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene. The protein encoded by this gene is a ubiquitously expressed nuclear protein. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the functions of BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants encoding two different isoforms have been found for this gene. More transcript variants exist, but their full-length natures have not been determined.
RBBP8 is an endonuclease that works with the MRE11-RAD50-NBN (MRN) complex to process DNA ends during the first step of double-strand break (DSB) repair through homologous recombination (HR). HR primarily occurs during the S and G2 phases of the cell cycle, particularly repairing DSBs caused by replication fork collapse. RBBP8 is crucial in directing DSB repair towards the HR pathway, preventing the use of the classical non-homologous end-joining (NHEJ) mechanism. It functions after the MRN complex and ATM, stimulating ATR activation and its recruitment to DSBs during S/G2, which aids in generating single-stranded DNA (ssDNA). As part of the BRCA1-RBBP8 complex, it regulates CHEK1 activation and controls cell cycle G2/M checkpoints in response to DNA damage. It plays a vital role in immunoglobulin heavy chain class-switch recombination, promoting microhomology-mediated alternative end joining (A-NHEJ) and influencing chromosomal translocations. RBBP8 has a preference for binding to DNA Y-junctions and DNA substrates with blocked ends, promoting intermolecular DNA bridging.
RBBP8 is also known as COM1, CTIP, JAWAD, JWDS, RIM, SAE2, SCKL2.
