Retinoblastoma-binding protein 8 (RBBP8)

Retinoblastoma-binding protein 8 (RBBP8) is a ubiquitously expressed nuclear endonuclease that plays a critical role in the repair of DNA double-strand breaks by homologous recombination, cooperating directly with the MRE11-RAD50-NBN (MRN) complex to process DNA ends for repair. RBBP8 helps determine the pathway choice between homologous recombination and non-homologous end joining, regulates key cell cycle transitions (G1/S and G2/M checkpoints), and complexes with key tumor suppressors including BRCA1 and transcriptional corepressors like CTBP. It is essential for genome stability and proper cellular proliferation, and its dysfunction is associated with cancer development, resistance to DNA-damaging chemotherapy, and inherited disorders such as Jawad syndrome and Seckel syndrome 2. RBBP8 is of therapeutic interest both as a determinant of cancer therapy response (notably to PARP inhibitors) and as a possible target for synthetic lethality strategies, particularly in cancers with homologous recombination defects.

Other names

CTIPCtIPDNA endonuclease RBBP8RIMSAE2COM1CTBP-interacting proteinJawad syndrome protein (JWDS)SCKL2Retinoblastoma-interacting protein and myosin-likeSporulation in the absence of SPO11 protein 2 homolog

Synthetic lethality with PARP inhibitors: loss of RBBP8 impairs homologous recombination, sensitizing cells to PARP inhibition.