XPC gene: MedlinePlus Genetics (original) (raw)
XPC complex subunit, DNA damage recognition and repair factor
Normal Function
The XPC gene provides instructions for making a protein that is involved in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from sunlight and by toxic chemicals, radiation, and unstable molecules called free radicals.
DNA damage occurs frequently, but normal cells are usually able to fix it before it can cause problems. One of the major mechanisms that cells use to fix DNA is known as nucleotide excision repair (NER). The XPC protein starts this repair process by detecting DNA damage. Then a group (complex) of other proteins unwind the section of DNA where the damage has occurred, snip out (excise) the abnormal section, and replace the damaged area with the correct DNA.
Studies suggest that the XPC protein may have additional roles in DNA repair and in other cell activities. Less is known about these proposed functions of the XPC protein.
Health Conditions Related to Genetic Changes
Xeroderma pigmentosum
Many variants (also called mutations) in the XPC gene have been found to cause xeroderma pigmentosum. People with this condition have an extreme sensitivity to UV rays from sunlight. As a result, affected individuals have a high risk of sunlight-induced cancer and premature aging.
Variants in the XPC gene are the most common cause of this disorder in the United States and Europe. Most XPC gene variants prevent the production of any XPC protein. A loss of this protein keeps cells from repairing DNA damage normally. As damage builds up in DNA, cells malfunction and eventually become cancerous or die.
These problems with DNA repair cause people with xeroderma pigmentosum to be extremely sensitive to UV rays. When UV rays damage genes that control cell growth and division, cells can grow too fast and in an uncontrolled way. This uncontrolled cell growth can lead to cancer. In people with xeroderma pigmentosum, cancers occur most frequently in areas of the body that are exposed to the sun, such as the skin and eyes.
Individuals with xeroderma pigmentosum caused by variants in the XPC gene may have an increased risk of early menopause compared to the general population. Unlike some of the other forms of xeroderma pigmentosum, when the disorder is caused by variants in the XPC gene it is generally not associated with neurological abnormalities (such as delayed development and hearing loss). It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.
More About This Health Condition
Other Names for This Gene
- RAD4
- Xeroderma pigmentosum group C-complementing protein
- xeroderma pigmentosum, complementation group C
- XP3
- XPC_HUMAN
- XPCC
References
- Bernardes de Jesus BM, Bjoras M, Coin F, Egly JM. Dissection of the molecular defects caused by pathogenic mutations in the DNA repair factor XPC. Mol Cell Biol. 2008 Dec;28(23):7225-35. doi: 10.1128/MCB.00781-08. Epub 2008 Sep 22. Citation on PubMed or Free article on PubMed Central
- Chavanne F, Broughton BC, Pietra D, Nardo T, Browitt A, Lehmann AR, Stefanini M. Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels. Cancer Res. 2000 Apr 1;60(7):1974-82. Citation on PubMed
- Cleaver JE, Thompson LH, Richardson AS, States JC. A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Hum Mutat. 1999;14(1):9-22. doi: 10.1002/(SICI)1098-1004(1999)14:13.0.CO;2-6. Citation on PubMed
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- Hoogstraten D, Bergink S, Ng JM, Verbiest VH, Luijsterburg MS, Geverts B, Raams A, Dinant C, Hoeijmakers JH, Vermeulen W, Houtsmuller AB. Versatile DNA damage detection by the global genome nucleotide excision repair protein XPC. J Cell Sci. 2008 Sep 1;121(Pt 17):2850-9. doi: 10.1242/jcs.031708. Epub 2008 Aug 5. Erratum In: J Cell Sci. 2008 Dec 1;121(Pt 23):3991. Ng, Jessica M Y [added]. J Cell Sci. 2008 Sep 1;121(Pt 17):2972. Citation on PubMed
- Khan SG, Oh KS, Shahlavi T, Ueda T, Busch DB, Inui H, Emmert S, Imoto K, Muniz-Medina V, Baker CC, DiGiovanna JJ, Schmidt D, Khadavi A, Metin A, Gozukara E, Slor H, Sarasin A, Kraemer KH. Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients. Carcinogenesis. 2006 Jan;27(1):84-94. doi: 10.1093/carcin/bgi204. Epub 2005 Aug 4. Citation on PubMed
- Sugasawa K. UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair. J Mol Histol. 2006 Sep;37(5-7):189-202. doi: 10.1007/s10735-006-9044-7. Epub 2006 Jul 21. Citation on PubMed
- Sugasawa K. XPC: its product and biological roles. Adv Exp Med Biol. 2008;637:47-56. doi: 10.1007/978-0-387-09599-8_6. Citation on PubMed