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REV1蛋白中的泛素结合基序对于其在DNA损伤耐受性中的作用是必需的。

Ubiquitin-binding motifs in REV1 protein are required for its role in the tolerance of DNA damage.

作者信息

Guo Caixia, Tang Tie-Shan, Bienko Marzena, Parker Joanne L, Bielen Aleksandra B, Sonoda Eiichiro, Takeda Shunichi, Ulrich Helle D, Dikic Ivan, Friedberg Errol C

机构信息

Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9072, USA.

出版信息

Mol Cell Biol. 2006 Dec;26(23):8892-900. doi: 10.1128/MCB.01118-06. Epub 2006 Sep 18.

Abstract

REV1 protein is a eukaryotic member of the Y family of DNA polymerases involved in the tolerance of DNA damage by replicative bypass. The precise role(s) of REV1 in this process is not known. Here we show, by using the yeast two-hybrid assay and the glutathione S-transferase pull-down assay, that mouse REV1 can physically interact with ubiquitin. The association of REV1 with ubiquitin requires the ubiquitin-binding motifs (UBMs) located at the C terminus of REV1. The UBMs also mediate the enhanced association between monoubiquitylated PCNA and REV1. In cells exposed to UV radiation, the association of REV1 with replication foci is dependent on functional UBMs. The UBMs of REV1 are shown to contribute to DNA damage tolerance and damage-induced mutagenesis in vivo.

摘要

REV1蛋白是DNA聚合酶Y家族的真核成员,参与通过复制性旁路耐受DNA损伤。REV1在此过程中的具体作用尚不清楚。在这里,我们通过酵母双杂交试验和谷胱甘肽S-转移酶下拉试验表明,小鼠REV1能与泛素发生物理相互作用。REV1与泛素的结合需要位于REV1 C末端的泛素结合基序(UBMs)。这些UBMs还介导了单泛素化PCNA与REV1之间增强的结合。在暴露于紫外线辐射的细胞中,REV1与复制灶的结合依赖于功能性UBMs。REV1的UBMs在体内有助于DNA损伤耐受和损伤诱导的诱变。

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