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The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis
Centre for Information Based Medicine, Hunter Medical Research Institute, and School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW 2289, Australia
* Author to whom correspondence should be addressed.
Received: 31 October 2012; in revised form: 29 November 2012 / Accepted: 26 December 2012 / Published: 9 January 2013
Abstract: UVB radiation is the most mutagenic component of the UV spectrum that reaches the earth’s surface and causes the development of DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts. UV radiation usually results in cellular death, but if left unchecked, it can affect DNA integrity, cell and tissue homeostasis and cause mutations in oncogenes and tumour-suppressor genes. These mutations, if unrepaired, can lead to abnormal cell growth, increasing the risk of cancer development. Epidemiological data strongly associates UV exposure as a major factor in melanoma development, but the exact biological mechanisms involved in this process are yet to be fully elucidated. The nucleotide excision repair (NER) pathway is responsible for the repair of UV-induced lesions. Patients with the genetic disorder Xeroderma Pigmentosum have a mutation in one of eight NER genes associated with the XP complementation groups XP-A to XP-G and XP variant (XP-V). XP is characterized by diminished repair capacity, as well as a 1000-fold increase in the incidence of skin cancers, including melanoma. This has suggested a significant role for NER in melanoma development as a result of UVB exposure. This review discusses the current research surrounding UVB radiation and NER capacity and how further investigation of NER could elucidate the role of NER in avoiding UV-induced cellular death resulting in melanomagenesis.
Keywords: ultraviolet light; UVB; DNA damage; 6-4 photoproducts; cyclobutane pyrimidine dimers; DNA repair; nucleotide excision repair; cell death; apoptosis; melanoma
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MDPI and ACS Style
Budden, T.; Bowden, N.A. The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis. Int. J. Mol. Sci. 2013, 14, 1132-1151.
Budden T, Bowden NA. The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis. International Journal of Molecular Sciences. 2013; 14(1):1132-1151.
Budden, Timothy; Bowden, Nikola A. 2013. "The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis." Int. J. Mol. Sci. 14, no. 1: 1132-1151.