Journal Article

UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2

Qi-En Wang, Qianzheng Zhu, Gulzar Wani, Jianming Chen and Altaf A. Wani

in Carcinogenesis

Volume 25, issue 6, pages 1033-1043
Published in print June 2004 | ISSN: 0143-3334
Published online June 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh085
UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2

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The tumor suppressor p53 protein has been established as an important factor in modulating the efficiency of global genomic repair. Our recent repair studies in human cells reported that p53 regulates the recruitment of XPC and TFIIH proteins to specific DNA damage sites. Here, we have examined the influence of p53 and damaged-DNA binding complex (DDB2) proteins on the distribution of XPC within damaged chromatin in vivo and the recruitment of XPC to DNA damage sites in situ. The results show that UV irradiation causes the translocation of XPC from a loosely bound form into a tight association with chromatin in vivo. The UV radiation-induced redistribution of XPC was equally compromised in p53-deficient, as well as DDB2-deficient, human cells. Similarly, rapid recruitment of XPC to DNA damage in situ was also impaired in both cell lines. Ectopic expression of DDB2 in p53-deficient cells overcame the requirement of p53 function for UV-induced translocation of XPC in vivo. Restoration of DDB2 function also enhanced the recruitment of XPC to DNA damage sites in situ and increased the global repair of cyclobutane pyrimidine dimer from the genome. These results indicate that DDB2 is a key downstream factor of p53 for regulating the movement of XPC to DNA damage in irradiated cells.

Keywords: CPD, cyclobutane pyrimidine dimer; DDB, damaged-DNA binding complex; GGR, global genome repair; LFS, Li-Fraumeni syndrome; NER, nucleotide excision repair; PBS, phosphate-buffered saline; 6–4PP, pyrimidine (6–4) pyrimidone photoproduct; TCR, transcription-coupled repair; XP, xeroderma pigmentosum

Journal Article.  8917 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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