Department of Chemistry & Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Molecules. 2019 Aug 1;24(15):2805. doi: 10.3390/molecules24152805.
DNA polymerase (pol) kappa is a Y-family translesion DNA polymerase conserved throughout all domains of life. Pol kappa is special6 ized for the ability to copy DNA containing minor groove DNA adducts, especially -dG adducts, as well as to extend primer termini containing DNA damage or mismatched base pairs. Pol kappa generally cannot copy DNA containing major groove modifications or UV-induced photoproducts. Pol kappa can also copy structured or non-B-form DNA, such as microsatellite DNA, common fragile sites, and DNA containing G quadruplexes. Thus, pol kappa has roles both in maintaining and compromising genomic integrity. The expression of pol kappa is altered in several different cancer types, which can lead to genome instability. In addition, many cancer-associated single-nucleotide polymorphisms have been reported in the gene, some of which are associated with poor survival and altered chemotherapy response. Because of this, identifying inhibitors of pol kappa is an active area of research. This review will address these activities of pol kappa, with a focus on lesion bypass and cellular mutagenesis.
DNA 聚合酶（pol）κ是一种 Y 家族的跨损伤 DNA 聚合酶，在所有生命领域中都得到了保守。pol κ的特殊之处在于能够复制含有小沟 DNA 加合物的 DNA，尤其是 -dG 加合物，以及延伸含有 DNA 损伤或错配碱基对的引物末端。pol κ通常不能复制含有大沟修饰或 UV 诱导的光产物的 DNA。pol κ还可以复制结构或非 B 型 DNA，如微卫星 DNA、常见脆性位点和含有 G 四联体的 DNA。因此，pol κ在维持和破坏基因组完整性方面都有作用。几种不同类型的癌症中 pol κ的表达发生了改变，这可能导致基因组不稳定。此外，在 基因中已经报道了许多与癌症相关的单核苷酸多态性，其中一些与不良预后和化疗反应改变有关。因此，鉴定 pol κ的抑制剂是一个活跃的研究领域。本综述将讨论 pol κ的这些活性，重点是损伤绕过和细胞诱变。
