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

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalGenes to Cells
Issue number2
Publication statusPublished - Feb 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology


Dive into the research topics of 'Role of DNA polymerase θ in tolerance of endogenous and exogenous DNA damage in mouse B cells'. Together they form a unique fingerprint.

Cite this