Gan Gregory N, Wittschieben John P, Wittschieben Birgitte Ø, Wood Richard D
Department of Pharmacology, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.
Cell Res. 2008 Jan;18(1):174-83. doi: 10.1038/cr.2007.117.
Most current knowledge about DNA polymerase zeta (pol zeta) comes from studies of the enzyme in the budding yeast Saccharomyces cerevisiae, where pol zeta consists of a complex of the catalytic subunit Rev3 with Rev7, which associates with Rev1. Most spontaneous and induced mutagenesis in yeast is dependent on these gene products, and yeast pol zeta can mediate translesion DNA synthesis past some adducts in DNA templates. Study of the homologous gene products in higher eukaryotes is in a relatively early stage, but additional functions for the eukaryotic proteins are already apparent. Suppression of vertebrate REV3L function not only reduces induced point mutagenesis but also causes larger-scale genome instability by raising the frequency of spontaneous chromosome translocations. Disruption of Rev3L function is tolerated in Drosophila, Arabidopsis, and in vertebrate cell lines under some conditions, but is incompatible with mouse embryonic development. Functions for REV3L and REV7(MAD2B) in higher eukaryotes have been suggested not only in translesion DNA synthesis but also in some forms of homologous recombination, repair of interstrand DNA crosslinks, somatic hypermutation of immunoglobulin genes and cell-cycle control. This review discusses recent developments in these areas.
目前关于DNA聚合酶ζ（pol ζ）的大部分知识来自对芽殖酵母酿酒酵母中该酶的研究，在酿酒酵母中，pol ζ由催化亚基Rev3与Rev7组成的复合物构成，Rev7与Rev1相关联。酵母中的大多数自发和诱导突变都依赖于这些基因产物，并且酵母pol ζ可以介导跨越DNA模板中某些加合物的跨损伤DNA合成。对高等真核生物中同源基因产物的研究尚处于相对早期阶段，但真核生物蛋白质的其他功能已经显现出来。抑制脊椎动物REV3L的功能不仅会减少诱导的点突变，还会通过提高自发染色体易位的频率导致更大规模的基因组不稳定。在某些条件下，果蝇、拟南芥和脊椎动物细胞系中Rev3L功能的破坏是可以耐受的，但与小鼠胚胎发育不兼容。高等真核生物中REV3L和REV7（MAD2B）的功能不仅在跨损伤DNA合成中，而且在某些形式的同源重组、链间DNA交联修复、免疫球蛋白基因的体细胞超突变和细胞周期控制中都有体现。本综述讨论了这些领域的最新进展。
