title: Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage.
abstract: Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H(2)O(2), but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLbeta. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLQ, like POLbeta, accumulated rapidly at sites of base damage. Accordingly, POLQ and POLbeta share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER.
authors.affiliation: Department of Radiation Genetics, CREST, Japan Science and Technology Laboratory, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Masaoki
authors.initials: M
authors.lastname: Kohzaki
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Asagoshi
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Sonoda
authors.forename: Esther
authors.initials: E
authors.lastname: Hou
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Wilson
authors.forename: Keizo
authors.initials: K
authors.lastname: Tano
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: Mineaki
authors.initials: M
authors.lastname: Seki
authors.forename: Richard D
authors.initials: RD
authors.lastname: Wood
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Buerstedde
authors.forename: Helfrid
authors.initials: H
authors.lastname: Hochegger
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002645:Chickens / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019951:DNA Polymerase beta / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009154:Mutation; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary; D014466:Ultraviolet Rays
chemical_list: D030161:Avian Proteins; D006861:Hydrogen Peroxide; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; D004265:DNA Helicases; D002945:Cisplatin