UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι

DNA Repair
Rie KanaoFumio Hanaoka

Abstract

Xeroderma pigmentosum variant (XP-V) is a human rare inherited recessive disease, predisposed to sunlight-induced skin cancer, which is caused by deficiency in DNA polymerase η (Polη). Polη catalyzes accurate translesion synthesis (TLS) past pyrimidine dimers, the most prominent UV-induced lesions. DNA polymerase ι (Polι) is a paralog of Polη that has been suggested to participate in TLS past UV-induced lesions, but its function in vivo remains uncertain. We have previously reported that Polη-deficient and Polη/Polι double-deficient mice showed increased susceptibility to UV-induced carcinogenesis. Here, we investigated UV-induced mutation frequencies and spectra in the epidermal cells of Polη- and/or Polι-deficient mice. While Polη-deficient mice showed significantly higher UV-induced mutation frequencies than wild-type mice, Polι deficiency did not influence the frequencies in the presence of Polη. Interestingly, the frequencies in Polη/Polι double-deficient mice were statistically lower than those in Polη-deficient mice, although they were still higher than those of wild-type mice. Sequence analysis revealed that most of the UV-induced mutations in Polη-deficient and Polη/Polι double-deficient mice were base substitutions at...Continue Reading

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Citations

Sep 16, 2015·The Journal of Biological Chemistry·Justyna McIntyreRoger Woodgate
Aug 2, 2018·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Leon H F Mullenders
May 26, 2020·Critical Reviews in Biochemistry and Molecular Biology·Huidong Zhang
Jun 30, 2019·Nucleic Acids Research·Bas PilzeckerHeinz Jacobs
Dec 20, 2019·Nucleic Acids Research·Natália Cestari MorenoCarlos Frederico Martins Menck

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