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Available structures
PDBOrtholog search: PDBe RCSB
AliasesXRCC1, RCC, X-ray repair complementing defective repair in Chinese hamster cells 1, X-ray repair cross complementing 1, SCAR26
External IDsOMIM: 194360 MGI: 99137 HomoloGene: 31368 GeneCards: XRCC1
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 19: 43.54 – 43.58 MbChr 7: 24.25 – 24.27 Mb
PubMed search[3][4]
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DNA repair protein XRCC1, also known as X-ray repair cross-complementing protein 1, is a protein that in humans is encoded by the XRCC1 gene. XRCC1 is involved in DNA repair, where it complexes with DNA ligase III.


nmr solution structure of the single-strand break repair protein xrcc1-n-terminal domain
Pfam clanCL0202
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary

XRCC1 is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis, i.e. during the induction of meiosis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity.[5]

The XRCC1 protein does not have enzymatic activity, but acts as a scaffolding protein that interacts with multiple repair enzymes. The scaffolding allows these repair enzymes to then carry out their enzymatic steps in repairing DNA. XRCC1 is involved in single-strand break repair, base excision repair and nucleotide excision repair.[6]

As reviewed by London,[6] XRCC1 protein has three globular domains connected by two linker segments of ~150 and 120 residues. The XRCC1 N-terminal domain binds to DNA polymerase beta, the C-terminal BRCT domain interacts with DNA ligase III alpha and the central domain contains a poly(ADP-ribose) binding motif. This central domain allows recruitment of XRCC1 to polymeric ADP-ribose that forms on PARP1 after PARP1 binds to single strand breaks. The first linker contains a nuclear localization sequence and also has a region that interacts with DNA repair protein REV1, and REV1 recruits translesion polymerases. The second linker interacts with polynucleotide kinase phosphatase ( PNKP) (that processes DNA broken ends during base excision repair), aprataxin (active in single-strand DNA repair and non-homologous end joining) and a third protein designated aprataxin- and PNKP-like factor.

XRCC1 has an essential role in microhomology-mediated end joining (MMEJ) repair of double strand breaks. MMEJ is a highly error-prone DNA repair pathway that results in deletion mutations. XRCC1 is one of 6 proteins required for this pathway.[7]

Over-expression in cancer[edit]

XRCC1 is over-expressed in non-small-cell lung carcinoma (NSCLC),[8] and at an even higher level in metastatic lymph nodes of NSCLC.[9]

Under-expression in cancer[edit]

Deficiency in XRCC1, due to being heterozygous for a mutated XRCC1 gene coding for a truncated XRCC1 protein, suppresses tumor growth in mice.[10] Under three experimental conditions for inducing three types of cancer (colon cancer, melanoma or breast cancer), mice heterozygous for this XRCC1 mutation had substantially lower tumor volume or number than wild type mice undergoing the same carcinogenic treatments.

Comparison with other DNA repair genes in cancer[edit]

Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is less usual in cancer. For instance, at least 36 DNA repair proteins, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary cancer syndromes).[citation needed] (Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers.[citation needed] (See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors (translesion synthesis), lead to mutations and cancer. However, XRCC1 mediated MMEJ repair is directly mutagenic, so in this case, over-expression, rather than under-expression, apparently leads to cancer. Reduction of mutagenic XRCC1 mediated MMEJ repair leads to reduced progression of cancer.


In aged human adipose-derived stem cells, base excision repair (BER), but not DNA double-strand break repair, is impaired. The XRCC1 protein, but not other BER factors, showed an age-associated decline.[11] Overexpression of XRCC1 reversed the age-associated decline of BER function.

Stroke recovery[edit]

Oxidative stress is increased in the brain during ischemic stroke leading to an increased burden on stress resistance mechanisms, including those for repairing oxidatively damaged DNA. Consequently any loss of a repair system that would ordinarily restore damaged DNA may impede survival and normal function of brain neurons. Ghosh et al.[12] reported that partial loss of XRCC1 function causes increased DNA damage in the brain and reduced recovery from ischemic stroke. This finding indicates that XRCC1-mediated base excision repair is important for speedy recovery from stroke.


The NMR solution structure of the Xrcc1 N-terminal domain (Xrcc1 NTD) shows that the structural core is a beta-sandwich with beta-strands connected by loops, three helices and two short two-stranded beta-sheets at each connection side. The Xrcc1 NTD specifically binds single-strand break DNA (gapped and nicked) and a gapped DNA-beta-Pol complex.[13]


XRCC1 has been shown to interact with:


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000073050Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000051768Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: XRCC1 X-ray repair complementing defective repair in Chinese hamster cells 1".
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  14. ^ Vidal AE, Boiteux S, Hickson ID, Radicella JP (Nov 2001). "XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions". The EMBO Journal. 20 (22): 6530–9. doi:10.1093/emboj/20.22.6530. PMC 125722. PMID 11707423.
  15. ^ Date H, Igarashi S, Sano Y, Takahashi T, Takahashi T, Takano H, Tsuji S, Nishizawa M, Onodera O (Dec 2004). "The FHA domain of aprataxin interacts with the C-terminal region of XRCC1". Biochemical and Biophysical Research Communications. 325 (4): 1279–85. doi:10.1016/j.bbrc.2004.10.162. PMID 15555565.
  16. ^ a b Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF (May 2004). "Aprataxin, a novel protein that protects against genotoxic stress". Human Molecular Genetics. 13 (10): 1081–93. doi:10.1093/hmg/ddh122. PMID 15044383.
  17. ^ Marsin S, Vidal AE, Sossou M, Ménissier-de Murcia J, Le Page F, Boiteux S, de Murcia G, Radicella JP (Nov 2003). "Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1". The Journal of Biological Chemistry. 278 (45): 44068–74. doi:10.1074/jbc.M306160200. PMID 12933815.
  18. ^ Schreiber V, Amé JC, Dollé P, Schultz I, Rinaldi B, Fraulob V, Ménissier-de Murcia J, de Murcia G (Jun 2002). "Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1" (PDF). The Journal of Biological Chemistry. 277 (25): 23028–36. doi:10.1074/jbc.M202390200. PMID 11948190.
  19. ^ a b Fan J, Otterlei M, Wong HK, Tomkinson AE, Wilson DM (2004). "XRCC1 co-localizes and physically interacts with PCNA". Nucleic Acids Research. 32 (7): 2193–201. doi:10.1093/nar/gkh556. PMC 407833. PMID 15107487.
  20. ^ Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko DD, Weinfeld M, Caldecott KW (Jan 2001). "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair". Cell. 104 (1): 107–17. doi:10.1016/S0092-8674(01)00195-7. PMID 11163244. S2CID 1487128.
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  22. ^ Wang L, Bhattacharyya N, Chelsea DM, Escobar PF, Banerjee S (Nov 2004). "A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype". Cancer Research. 64 (21): 7673–7. doi:10.1158/0008-5472.CAN-04-2801. PMID 15520167. S2CID 35569215.
  23. ^ Kubota Y, Nash RA, Klungland A, Schär P, Barnes DE, Lindahl T (Dec 1996). "Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein". The EMBO Journal. 15 (23): 6662–70. doi:10.1002/j.1460-2075.1996.tb01056.x. PMC 452490. PMID 8978692.
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Further reading[edit]

External links[edit]

This article incorporates text from the public domain Pfam and InterPro: IPR002706