DNA repair protein XRCC1 (XRCC1)

DNA repair protein XRCC1 (X-ray repair cross-complementing protein 1) is a central scaffold protein in the repair of DNA single-strand breaks and base excision repair (BER)[1][2][4][5]. XRCC1 lacks enzymatic activity; instead, it coordinates and facilitates repair by binding and assembling key enzymes such as DNA ligase III, DNA polymerase β, poly(ADP-ribose) polymerase (PARP1), and additional partners involved in direct DNA repair and translesion synthesis[1][4]. XRCC1 is recruited to sites of DNA damage, in part via interactions with poly(ADP-ribose) generated by PARP, and organizes repair complexes to efficiently process DNA lesions arising from oxidative stress, irradiation, or alkylating agents[2][4]. Loss or dysfunction of XRCC1 leads to defective DNA repair capacity, hypersensitivity to DNA-damaging agents, increased genomic instability, and is associated with disease susceptibility, including cancer and neurodegenerative disorders[1][2][5]. XRCC1 is considered a key modulator of cellular responses to DNA damage and plays a contributory role in therapeutic response and resistance, making it a significant biomarker and potential therapeutic co-target in precision medicine approaches[1][2][4][5].

Other names

X-ray repair cross-complementing protein 1X-ray repair cross complementing 1RCCSCAR26DNA repair protein XRCC1X-ray repair complementing defective repair in Chinese hamster cells 1

Drugs do not (as of current knowledge) directly target XRCC1, but resistance/sensitivity mechanisms involve: DNA damage induction and repair modulation; PARP inhibitor-induced lethality in defective repair backgrounds; Potential future approaches: Direct disruption of protein-protein interactions within XRCC1 repair complexes.