XRCC1

DNA repair protein XRCC1 also known as X-ray repair cross-complementing protein 1 is a is_associated_with::protein that in humans is encoded by the XRCC1 is_associated_with::gene. XRCC1 is involved in is_associated_with::DNA repair where it complexes with is_associated_with::DNA ligase III.

Function
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 is_associated_with::base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity.

Other function of XRCC1
In addition to its role in base excision repair, XRCC1 also has an essential role in is_associated_with::microhomology-mediated end joining (MMEJ) repair of double strand breaks. MMEJ is an error-prone DNA repair pathway that results in deletion mutations. XRCC1 is one of 6 proteins required for this pathway.

XRCC1 over-expression in cancer
XRCC1 is over-expressed in is_associated_with::non-small-cell lung carcinoma (NSCLC), and at an even higher level in metastatic lymph nodes of NSCLC.

XRCC1 under-expression in cancer
Deficiency in XRCC1, due to being heterozygous for a mutated XRCC1 gene coding for a truncated XRCC1 protein, suppresses tumor growth in mice. 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
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 is_associated_with::cancer syndromes). (Also see is_associated_with::DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers. (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.

Structure
The NMR solution structure of the Xrcc1 is_associated_with::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 is_associated_with::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.

Interactions
XRCC1 has been shown to interact with:


 * is_associated_with::APEX1,
 * APTX,
 * OGG1,
 * is_associated_with::PARP2,
 * is_associated_with::PCNA,
 * is_associated_with::PNKP,
 * POLB,   and
 * is_associated_with::PARP1.