title: WRNIP1 functions upstream of DNA polymerase η in the UV-induced DNA damage response.
abstract: WRNIP1 (WRN-interacting protein 1) was first identified as a factor that interacts with WRN, the protein that is defective in Werner syndrome (WS). WRNIP1 associates with DNA polymerase η (Polη), but the biological significance of this interaction remains unknown. In this study, we analyzed the functional interaction between WRNIP1 and Polη by generating knockouts of both genes in DT40 chicken cells. Disruption of WRNIP1 in Polη-disrupted (POLH(-/-)) cells suppressed the phenotypes associated with the loss of Polη: sensitivity to ultraviolet light (UV), delayed repair of cyclobutane pyrimidine dimers (CPD), elevated frequency of mutation, elevated levels of UV-induced sister chromatid exchange (SCE), and reduced rate of fork progression after UV irradiation. These results suggest that WRNIP1 functions upstream of Polη in the response to UV irradiation.
authors.affiliation: Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Electronic address: akari_yo@stu.musashino-u.ac.jp.
authors.forename: Akari
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Yume
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Medical Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Tada
authors.affiliation: Department of Biochemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai-shi, Miyagi 981-8558, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.affiliation: Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases; C430237:WRNIP1 protein, human
keywords: DNA polymerase eta; TLS; WRNIP1