Impaired Repair of Cyclobutane Pyrimidine Dimers in Human Keratinocytes Deficient in P53 and P63

Overview

Journal Carcinogenesis

Specialty Oncology

Date 2007 Nov 7

PMID 17984111

Citations 11

Authors

Bridget E Ferguson-Yates

Hongyan Li

Tiffany K Dong

Jennifer L Hsiao

Dennis H Oh

Affiliations

Soon will be listed here.

Abstract

While many p53-deficient cell types are impaired in global genomic nucleotide excision repair of cyclobutane pyrimidine dimers (CPDs), human epidermal keratinocytes expressing human papillomavirus type 16 E6 and E7 are p53 deficient and yet maintain repair of CPD. We hypothesized that the p53 homolog, p63, may participate in governing global repair instead of p53 in keratinocytes. Following ultraviolet radiation (UVR) of E6/E7 keratinocytes, depletion of p63 but not of p73 impaired global genomic repair of CPD relative to control cells. In all cases, repair of pyrimidine(6-4)pyrimidone photoproducts, the other major UVR-induced DNA lesions, was unaffected. In E6/E7 keratinocytes treated with p63 small interfering RNA, reduced global repair of CPD was associated not with reduced levels of messenger RNA-encoding DNA damage recognition proteins but rather with decreased levels of DDB2 and XPC proteins, suggesting that p63 posttranscriptionally regulates levels of these proteins. These results indicate that global repair may be regulated at multiple levels and suggest a novel role for p63 in modulating repair of DNA damage in human keratinocytes. The results may provide insight into mechanisms of genomic stability in epithelia infected with oncogenic human papilloma viruses and may further explain the lack of increased skin cancer incidence in Li-Fraumeni syndrome.

Citing Articles

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Xu Y, Yang X, Xiong Q, Han J, Zhu Q Front Oncol. 2023; 13:1116061.

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Reduction of DNA damage repair efficiency and accumulation of residual damage following chronic UVB-irradiation of HaCaT cells.

Dorr M, Rochette P PLoS One. 2023; 18(4):e0283572.

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Xeroderma Pigmentosum C: A Valuable Tool to Decipher the Signaling Pathways in Skin Cancers.

Nasrallah A, Fayyad N, Kobaisi F, Badran B, Fayyad-Kazan H, Fayyad-Kazan M Oxid Med Cell Longev. 2021; 2021:6689403.

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Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity.

Kobaisi F, Fayyad N, Rezvani H, Fayyad-Kazan M, Sulpice E, Badran B Oxid Med Cell Longev. 2019; 2019:4654206.

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The interplay of UV and cutaneous papillomavirus infection in skin cancer development.

Hasche D, Stephan S, Braspenning-Wesch I, Mikulec J, Niebler M, Grone H PLoS Pathog. 2017; 13(11):e1006723.

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