WRNIP1 functions upstream of DNA polymerase η in the UV-induced DNA damage response

被引:8
作者
Yoshimura, Akari [1 ]
Kobayashi, Yume [1 ]
Tada, Shusuke [3 ]
Seki, Masayuki [2 ]
Enomoto, Takemi [1 ]
机构
[1] Musashino Univ, Fac Pharm, Pharmaceut Sci Res Inst, Mol Cell Biol Lab, Nishitokyo, Tokyo 2028585, Japan
[2] Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan
[3] Toho Univ, Fac Pharmaceut Sci, Dept Med Biochem, Funabashi, Chiba 2748510, Japan
基金
日本学术振兴会;
关键词
WRNIP1; DNA polymerase eta; TLS; TRANSLESION SYNTHESIS; PCNA; UBIQUITIN; REPAIR; DELTA; MGS1; PHOTOPRODUCTS; DEFICIENT; INTERACTS; PRODUCT;
D O I
10.1016/j.bbrc.2014.08.043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 eta (Pol eta), but the biological significance of this interaction remains unknown. In this study, we analyzed the functional interaction between WRNIP1 and Pol eta by generating knockouts of both genes in DT40 chicken cells. Disruption of WRNIP1 in Pol eta-disrupted (POLH-/-) cells suppressed the phenotypes associated with the loss of Pol eta: 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 Pol eta in the response to UV irradiation. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:48 / 52
页数:5
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