Guo Caixia, Sonoda Eiichiro, Tang Tie-Shan, Parker Joanne L, Bielen Aleksandra B, Takeda Shunichi, Ulrich Helle D, Friedberg Errol C
Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Mol Cell. 2006 Jul 21;23(2):265-71. doi: 10.1016/j.molcel.2006.05.038.
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.
REV1蛋白是DNA聚合酶Y家族的真核成员，通过跨损伤DNA合成参与DNA损伤耐受。目前尚不清楚REV1如何在细胞中被招募到复制位点。在此，我们报道小鼠REV1可直接与增殖细胞核抗原（PCNA）结合，且PCNA的单泛素化增强了这种相互作用。REV1蛋白与PCNA之间的相互作用需要位于前者蛋白质N端附近的功能性BRCT结构域。BRCT结构域的缺失或突变失活消除了REV1在未受辐射细胞中靶向复制位点的能力，但在紫外线照射的细胞中则不然。在鸡DT40细胞和酵母中的体内研究直接支持了REV1的BRCT结构域对细胞存活和DNA损伤诱导的诱变的必要性。
