The human gene that encodes XRCC1 was cloned nearly thirty years ago but experimental analysis of this fascinating protein is still unveiling new insights into the DNA damage response. XRCC1 is a molecular scaffold protein that interacts with multiple enzymatic components of DNA single-strand break repair (SSBR) including DNA kinase, DNA phosphatase, DNA polymerase, DNA deadenylase, and DNA ligase activities that collectively are capable of accelerating the repair of a broad range of DNA single-strand breaks (SSBs). Arguably the most exciting aspect of XRCC1 function that has emerged in the last few years is its intimate relationship with PARP1 activity and critical role in preventing hereditary neurodegenerative disease. Here, I provide an update on our current understanding of XRCC1, and on the impact of hereditary mutations in this protein and its protein partners on human disease.

Genome Damage and Stability Centre School of Life Sciences Falmer Brighton BN1 9RQ United Kingdom; Department of Genome Dynamics Institute of Molecular Genetics of the Czech Academy of Sciences 142 20 Prague 4 Czech Republic

References provided by Crossref.org

Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs

XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair

Parp1 hyperactivity couples DNA breaks to aberrant neuronal calcium signalling and lethal seizures

Neuronal enhancers are hotspots for DNA single-strand break repair

Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair