REV1 protein interacts with PCNA: Significance of the REV1 BRCT domain in vitro and in vivo
REV1 protein interacts with PCNA: Significance of the REV1 BRCT domain in vitro and in vivo
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DOI：
10.1016/j.molcel.2006.05.038
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发表时间：
2006-07-21
期刊：
影响因子：
16
通讯作者：
Friedberg, Errol C.
中科院分区：
文献类型：
--
作者：
Guo, Caixia;Sonoda, Eiichiro;Friedberg, Errol C.
REV1蛋白是DNA聚合酶Y家族的真核成员，参与通过跨损伤DNA合成对DNA损伤的耐受。目前尚不清楚REV1是如何被招募到细胞中的复制焦点的。在此，我们报道小鼠REV1能够直接与增殖细胞核抗原（PCNA）结合，并且PCNA的单泛素化增强这种相互作用。REV1蛋白与PCNA之间的相互作用需要位于前者蛋白N末端附近的一个有功能的BRCT结构域。BRCT结构域的缺失或突变失活会消除REV1在未受辐射细胞中靶向复制焦点的能力，但在紫外线照射的细胞中不会。在鸡DT40细胞和酵母中的体内研究直接支持REV1的BRCT结构域对于细胞存活和DNA损伤诱导的突变发生的必要性。
REV1 protein, a eukaryotic member of the Y family of DNA polymerases, is involved in the tolerance of DNA damage by translesion DNA synthesis. It is unclear how REV1 is recruited to replication foci in cells. Here, we report that mouse REV1 can bind directly to PCNA and that monoubiquitylation of PCNA enhances this interaction. The interaction between REV1 protein and PCNA requires a functional BRCT domain located near the N terminus of the former protein. Deletion or mutational inactivation of the BRCT domain abolishes the targeting of REV1 to replication foci in unirradiated cells, but not in UV-irradiated cells. In vivo studies in both chicken DT40 cells and yeast directly support the requirement of the BRCT domain of REV1 for cell survival and DNA damage-induced mutagenesis.