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

Rie Kanao, Masayuki Yokoi, Tsuyoshi Ohkumo, Yasutaka Sakurai, Kantaro Dotsu, Shinobu Kura, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Chikahide Masutani, Fumio Hanaoka

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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 dipyrimidine sites. An increase in UV-induced mutations at both G:C and A:T pairs associated with Polη deficiency suggests that Polη contributes to accurate TLS past both thymine- and cytosine-containing dimers in vivo. A significant decrease in G:C to A:T transition in Polη/Polι double-deficient mice when compared with Polη-deficient mice suggests that Polι is involved in error-prone TLS past cytosine-containing dimers when Polη is inactivated.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalDNA Repair
Volume29
DOIs
Publication statusPublished - May 1 2015

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kanao, R., Yokoi, M., Ohkumo, T., Sakurai, Y., Dotsu, K., Kura, S., ... Hanaoka, F. (2015). UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι. DNA Repair, 29, 139-146. https://doi.org/10.1016/j.dnarep.2015.02.006