Role of DNA polymerase θ in tolerance of endogenous and exogenous DNA damage in mouse B cells

Akiko Ukai, Takako Maruyama, Shigenobu Mochizuki, Rika Ouchida, Keiji Masuda, Kiyoko Kawamura, Masatoshi Tagawa, Kazuo Kinoshita, Akemi Sakamoto, Takeshi Tokuhisa, Jiyang O-Wang

研究成果: ジャーナルへの寄稿学術誌査読

26 被引用数 (Scopus)

抄録

DNA polymerase θ (Polθ) is a family A polymerase that contains an intrinsic helicase domain. To investigate the function of Polθ in mammalian cells, we have inactivated its polymerase activity in CH12 mouse B lymphoma cells by targeted deletion of the polymerase core domain that contains the catalytic aspartic acid residue. Compared to parental CH12 cells, mutant cells devoid of Polθ polymerase activity exhibited a slightly reduced growth rate, accompanied by increased spontaneous cell death. In addition, mutant cells showed elevated sensitivity to mitomycin C, cisplatin, etoposide, γ-irradiation and ultraviolet (UV) radiation. Interestingly, mutant cells were more sensitive to the alkylating agent methyl methanesulfonate (MMS) than parental cells. This elevated MMS sensitivity relative to WT cells persisted in the presence of methoxyamine, an inhibitor of the major base excision repair (BER) pathway, suggesting that Polθ is involved in tolerance of MMS through a mechanism that appears to be different from BER. These results reveal an important role for Polθ in preventing spontaneous cell death and in tolerance of not only DNA interstrand cross-links and double strand breaks but also UV adducts and alkylation damage in mammalian lymphocytes.

本文言語英語
ページ(範囲)111-121
ページ数11
ジャーナルGenes to Cells
11
2
DOI
出版ステータス出版済み - 2月 2006
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 細胞生物学

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