X-ray repair cross-complementing protein 1 (XRCC1)

X-ray repair cross-complementing protein 1 (XRCC1) is a vital molecular scaffold protein that coordinates the repair of DNA single-strand breaks and base damage through the base excision repair (BER) and single-strand break repair (SSBR) pathways [1, 8]. Although it lacks intrinsic enzymatic activity, XRCC1 facilitates the assembly of multi-protein repair complexes by interacting with key enzymes such as DNA polymerase beta, DNA ligase III alpha, and poly(ADP-ribose) polymerase 1 (PARP1) [10, 11]. In oncology, XRCC1 is frequently overexpressed in various tumors, where it contributes to resistance against radiation and chemotherapy by enhancing the cell's ability to repair treatment-induced DNA damage [12, 16]. Conversely, XRCC1 deficiency creates a therapeutic window for synthetic lethality, particularly when combined with PARP inhibitors, as it leads to the accumulation of toxic DNA lesions [3, 12]. Beyond its role in cancer, germline mutations in XRCC1 are linked to hereditary neurodegenerative disorders like spinocerebellar ataxia, underscoring its fundamental importance in maintaining genomic stability across different tissues [1, 6].

Other names

XRCC1RCCX-ray repair complementing defective repair in Chinese hamster cells 1X-ray repair cross complementing 1SCAR26

Inhibition of DNA repair pathways to sensitize cancer cells to DNA-damaging agents; synthetic lethality in combination with PARP inhibitors; promotion of trapped PARP1 removal from DNA.