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在酿酒酵母体内,TT光产物位点处紫外线诱导的T到C的转换依赖于DNA聚合酶η。

UV-induced T-->C transition at a TT photoproduct site is dependent on Saccharomyces cerevisiae polymerase eta in vivo.

作者信息

Zhang Hong, Siede Wolfram

机构信息

Department of Radiation Oncology and Winship Cancer Institute, B5111, Emory University School of Medicine, 1365 B Clifton Road NE, Atlanta, GA 30322, USA.

出版信息

Nucleic Acids Res. 2002 Mar 1;30(5):1262-7. doi: 10.1093/nar/30.5.1262.

Abstract

UV-induced reversion of the arg4-17 ochre allele in Saccharomyces cerevisiae is largely dependent on translesion polymerase eta (Rad30p), known to bypass cyclobutane-type TT dimers in an error-free fashion. arg4-17 locus reversion was predominantly due to T-->C transition of T127, the 3' T of a TT photoproduct site. This event was at least 20-fold reduced in a rad30 deletion mutant, irrespective of the status of nucleotide excision repair. These data correlate with known properties of 6-4 TT photoproducts and in vitro characteristics of polymerase eta and suggest that polymerase eta plays an important in vivo role in inserting G opposite the 3' T of 6-4 TT photoproducts at this site. Alternatively, an unprecedented error-prone processing of cyclobutane-type photoproducts at this site by polymerase eta must be assumed as the critical mechanism. Whereas photoreactivation results indeed hint at the latter possibility, a possible regulatory influence of reducing the overall UV damage load on the bypass probability of non-cyclobutane-type pyrimidine dimer photoproducts should not be dismissed.

摘要

紫外线诱导的酿酒酵母中arg4 - 17赭石型等位基因的回复突变很大程度上依赖于跨损伤聚合酶η(Rad30p),已知该酶能以无差错的方式绕过环丁烷型TT二聚体。arg4 - 17位点的回复突变主要是由于TT光产物位点3'端的T127发生T→C转换。无论核苷酸切除修复的状态如何,在rad30缺失突变体中,这一事件至少减少了20倍。这些数据与6 - 4 TT光产物的已知特性以及聚合酶η的体外特性相关,并表明聚合酶η在体内在此位点将G插入6 - 4 TT光产物3'端的T对面起着重要作用。或者,必须假定聚合酶η在此位点对环丁烷型光产物进行前所未有的易错处理是关键机制。虽然光复活的结果确实暗示了后一种可能性,但不应忽视降低总体紫外线损伤负荷对非环丁烷型嘧啶二聚体光产物绕过概率的可能调节影响。

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