p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo - PubMed (original) (raw)
Case Reports
p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo
Maureen E Fitch et al. Carcinogenesis. 2003 May.
Abstract
The p53 tumor suppressor gene is an important mediator of the cellular response to ultraviolet (UV)-irradiation-induced DNA damage and affects the efficiency of the nucleotide excision repair (NER) pathway. The mechanism by which p53 regulates NER may be through its ability to act as a transcription factor, and/or through direct interactions with damaged DNA or the repair machinery. p53 has been shown to regulate the expression of the DDB2 gene (encoding the p48 protein) and the XPC gene, two important components of the NER pathway involved in DNA damage recognition. In this study, a localized UV-irradiation technique was used to examine the localization of p53, p48 and XPC proteins in relation to sites of UV photoproducts, in vivo. We did not observe any specific co-localization of p53 with sites of UV-induced DNA damage, but did observe rapid co-localization of both p48 and XPC to these sites. p48 bound to UV photoproducts in cells mutant or deficient for either p53, XPC or XPA, and p48 enhanced XPC binding to lesions, suggesting that p48 is a very early recognition factor of DNA damage. We propose that p53 functions to transcriptionally regulate the DDB2 and XPC NER genes, but does not activate the NER pathway through direct interactions with UV-induced damaged DNA or other repair factors.
Similar articles
- Tumor suppressor p53 dependent recruitment of nucleotide excision repair factors XPC and TFIIH to DNA damage.
Wang QE, Zhu Q, Wani MA, Wani G, Chen J, Wani AA. Wang QE, et al. DNA Repair (Amst). 2003 May 13;2(5):483-99. doi: 10.1016/s1568-7864(03)00002-8. DNA Repair (Amst). 2003. PMID: 12713809 - The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts.
Fitch ME, Cross IV, Turner SJ, Adimoolam S, Lin CX, Williams KG, Ford JM. Fitch ME, et al. DNA Repair (Amst). 2003 Jul 16;2(7):819-26. doi: 10.1016/s1568-7864(03)00066-1. DNA Repair (Amst). 2003. PMID: 12826282 - In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.
Fitch ME, Nakajima S, Yasui A, Ford JM. Fitch ME, et al. J Biol Chem. 2003 Nov 21;278(47):46906-10. doi: 10.1074/jbc.M307254200. Epub 2003 Aug 27. J Biol Chem. 2003. PMID: 12944386 - Mechanism and regulation of DNA damage recognition in mammalian nucleotide excision repair.
Sugasawa K. Sugasawa K. Enzymes. 2019;45:99-138. doi: 10.1016/bs.enz.2019.06.004. Epub 2019 Jul 8. Enzymes. 2019. PMID: 31627884 Review. - Molecular mechanisms of DNA damage recognition for mammalian nucleotide excision repair.
Sugasawa K. Sugasawa K. DNA Repair (Amst). 2016 Aug;44:110-117. doi: 10.1016/j.dnarep.2016.05.015. Epub 2016 May 20. DNA Repair (Amst). 2016. PMID: 27264556 Review.
Cited by
- A novel DDB2 mutation causes defective recognition of UV-induced DNA damages and prevalent equine squamous cell carcinoma.
Chen L, Bellone RR, Wang Y, Singer-Berk M, Sugasawa K, Ford JM, Artandi SE. Chen L, et al. DNA Repair (Amst). 2021 Jan;97:103022. doi: 10.1016/j.dnarep.2020.103022. Epub 2020 Nov 12. DNA Repair (Amst). 2021. PMID: 33276309 Free PMC article. - In Situ Analysis of DNA-Protein Complex Formation upon Radiation-Induced DNA Damage.
Ticli G, Prosperi E. Ticli G, et al. Int J Mol Sci. 2019 Nov 15;20(22):5736. doi: 10.3390/ijms20225736. Int J Mol Sci. 2019. PMID: 31731696 Free PMC article. Review. - cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.
Holcomb NC, Bautista RM, Jarrett SG, Carter KM, Gober MK, D'Orazio JA. Holcomb NC, et al. Adv Protein Chem Struct Biol. 2019;115:247-295. doi: 10.1016/bs.apcsb.2018.10.008. Epub 2018 Dec 5. Adv Protein Chem Struct Biol. 2019. PMID: 30798934 Free PMC article. Review. - Effects and Mechanism of Nicotinamide Against UVA- and/or UVB-mediated DNA Damages in Normal Melanocytes.
Chhabra G, Garvey DR, Singh CK, Mintie CA, Ahmad N. Chhabra G, et al. Photochem Photobiol. 2019 Jan;95(1):331-337. doi: 10.1111/php.12994. Epub 2018 Sep 21. Photochem Photobiol. 2019. PMID: 30102774 Free PMC article. - SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes.
Calapre L, Gray ES, Kurdykowski S, David A, Descargues P, Ziman M. Calapre L, et al. BMC Dermatol. 2017 Jun 10;17(1):8. doi: 10.1186/s12895-017-0060-y. BMC Dermatol. 2017. PMID: 28601088 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous