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

Research output: Contribution to journalArticle

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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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DNA-Directed DNA Polymerase
Cells
Mutation
Cytosine
Dimers
Pyrimidine Dimers
Thymine
Mutation Rate
Skin
Substitution reactions
Sunlight
Skin Neoplasms
Sequence Analysis
Carcinogenesis

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

UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι. / Kanao, Rie; Yokoi, Masayuki; Ohkumo, Tsuyoshi; Sakurai, Yasutaka; Dotsu, Kantaro; Kura, Shinobu; Nakatsu, Yoshimichi; Tsuzuki, Teruhisa; Masutani, Chikahide; Hanaoka, Fumio.

In: DNA Repair, Vol. 29, 01.05.2015, p. 139-146.

Research output: Contribution to journalArticle

Kanao, R, Yokoi, M, Ohkumo, T, Sakurai, Y, Dotsu, K, Kura, S, Nakatsu, Y, Tsuzuki, T, Masutani, C & Hanaoka, F 2015, 'UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι', DNA Repair, vol. 29, pp. 139-146. https://doi.org/10.1016/j.dnarep.2015.02.006
Kanao, Rie ; Yokoi, Masayuki ; Ohkumo, Tsuyoshi ; Sakurai, Yasutaka ; Dotsu, Kantaro ; Kura, Shinobu ; Nakatsu, Yoshimichi ; Tsuzuki, Teruhisa ; Masutani, Chikahide ; Hanaoka, Fumio. / UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι. In: DNA Repair. 2015 ; Vol. 29. pp. 139-146.
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AU - Dotsu, Kantaro

AU - Kura, Shinobu

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