DNA 聚合酶θ对基因组的保护作用。
Genome Protection by DNA Polymerase θ.
机构信息
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Center, Houston, Texas, USA; email:
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA; email:
出版信息
Annu Rev Genet. 2022 Nov 30;56:207-228. doi: 10.1146/annurev-genet-072920-041046. Epub 2022 Aug 26.
DNA polymerase θ (Pol θ) is a DNA repair enzyme widely conserved in animals and plants. Pol θ uses short DNA sequence homologies to initiate repair of double-strand breaks by theta-mediated end joining. The DNA polymerase domain of Pol θ is at the C terminus and is connected to an N-terminal DNA helicase-like domain by a central linker. Pol θ is crucial for maintenance of damaged genomes during development, protects DNA against extensive deletions, and limits loss of heterozygosity. The cost of using Pol θ for genome protection is that a few nucleotides are usually deleted or added at the repair site. Inactivation of Pol θ often enhances the sensitivity of cells to DNA strand-breaking chemicals and radiation. Since some homologous recombination-defective cancers depend on Pol θ for growth, inhibitors of Pol θ may be useful in treating such tumors.
DNA 聚合酶 θ（Pol θ）是一种在动物和植物中广泛保守的 DNA 修复酶。Pol θ 通过θ介导的末端连接，利用短的 DNA 序列同源性来启动双链断裂的修复。Pol θ 的 DNA 聚合酶结构域位于 C 末端，通过中央接头与 N 末端 DNA 解旋酶样结构域相连。Pol θ 对于发育过程中受损基因组的维持至关重要，它可以防止 DNA 发生广泛缺失，并限制杂合性丢失。Pol θ 用于保护基因组的代价是修复位点通常会缺失或添加几个核苷酸。Pol θ 的失活通常会增加细胞对 DNA 链断裂化学物质和辐射的敏感性。由于一些同源重组缺陷型癌症的生长依赖于 Pol θ，因此 Pol θ 的抑制剂可能对治疗此类肿瘤有用。
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