Beagan Kelly, McVey Mitch
Department of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA, 02155, USA.
Cell Mol Life Sci. 2016 Feb;73(3):603-15. doi: 10.1007/s00018-015-2078-9. Epub 2015 Oct 29.
DNA polymerase theta (Pol θ) is an error-prone A-family polymerase that is highly conserved among multicellular eukaryotes and plays multiple roles in DNA repair and the regulation of genome integrity. Studies conducted in several model organisms have shown that Pol θ can be utilized during DNA interstrand crosslink repair and during alternative end-joining repair of double-strand breaks. Recent genetic and biochemical studies have begun to elucidate the unique structural features of Pol θ that promote alternative end-joining repair. Importantly, Pol θ-dependent end joining appears to be important for overall genome stability, as it affects chromosome translocation formation in murine and human cell lines. Pol θ has also been suggested to act as a modifier of replication timing in human cells, though the mechanism of action remains unknown. Pol θ is highly upregulated in a number of human cancer types, which could indicate that mutagenic Pol θ-dependent end joining is used during cancer cell proliferation. Here, we review the various roles of Pol θ across species and discuss how these roles may be relevant to cancer therapy.
DNA聚合酶θ（Pol θ）是一种易出错的A家族聚合酶，在多细胞真核生物中高度保守，在DNA修复和基因组完整性调控中发挥多种作用。在几种模式生物中进行的研究表明，Pol θ可用于DNA链间交联修复和双链断裂的替代末端连接修复。最近的遗传和生化研究已开始阐明促进替代末端连接修复的Pol θ的独特结构特征。重要的是，依赖Pol θ的末端连接似乎对整体基因组稳定性很重要，因为它会影响小鼠和人类细胞系中染色体易位的形成。尽管作用机制尚不清楚，但也有人提出Pol θ在人类细胞中作为复制时间的调节剂。Pol θ在多种人类癌症类型中高度上调，这可能表明在癌细胞增殖过程中使用了诱变的依赖Pol θ的末端连接。在此，我们综述了Pol θ在不同物种中的各种作用，并讨论了这些作用如何可能与癌症治疗相关。
