Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, PO Box 9600, 2300 RC Leiden, The Netherlands.
DNA Repair (Amst). 2009 Dec 3;8(12):1444-51. doi: 10.1016/j.dnarep.2009.09.006. Epub 2009 Sep 27.
DNA polymerase zeta is believed to be an essential constituent of DNA damage tolerance, comprising several pathways that allow the replication of DNA templates containing unrepaired damage. We wanted to better define the role of polymerase zeta in DNA damage tolerance in mammalian cells. To this aim we have investigated replication of ultraviolet light-damaged DNA templates in mouse embryonic fibroblasts deficient for Rev3, the catalytic subunit of polymerase zeta. We found that Rev3 is important for a post-replication repair pathway of helix-distorting [6-4]pyrimidine-pyrimidone photoproducts and, to a lesser extent, of cyclobutane pyrimidine dimers. Unlike its partner Rev1, Rev3 appears not to be involved in an immediate translesion synthesis pathway at a stalled replication fork. The deficiency of Rev3(-/-) MEFs in post-replication repair of different photoproducts contributes to the extreme sensitivity of these cells to UV light.
DNA 聚合酶 zeta 被认为是 DNA 损伤耐受的一个重要组成部分，它包含几个途径，允许复制含有未修复损伤的 DNA 模板。我们希望更好地定义聚合酶 zeta 在哺乳动物细胞 DNA 损伤耐受中的作用。为此，我们研究了紫外线损伤 DNA 模板在缺乏聚合酶 zeta 催化亚基 Rev3 的小鼠胚胎成纤维细胞中的复制。我们发现 Rev3 对扭曲螺旋的[6-4]嘧啶-嘧啶酮光产物的复制后修复途径很重要，对环丁烷嘧啶二聚体的重要性较小。与它的搭档 Rev1 不同，Rev3 似乎不参与停滞复制叉的即时跨损伤合成途径。Rev3(-/-) MEF 在不同光产物的复制后修复中的缺陷导致这些细胞对 UV 光极其敏感。
