DNA聚合酶θ对基因组的保护。
Genome Protection by DNA Polymerase θ.
发表日期:2022 Nov 30
作者:
Richard D Wood, Sylvie Doublié
来源:
Annual Review of Genetics
摘要:
DNA聚合酶θ(Pol θ)是广泛存在于动植物中的一种DNA修复酶。Pol θ利用短的DNA同源序列启动theta介导的端联合修复双链断裂。Pol θ的DNA聚合酶结构域位于C端,中央连接子将其连接到N端的DNA解旋酶样结构域。Pol θ对于维护受损基因组在发育过程中至关重要,保护DNA免受广泛缺失并限制杂合性丧失。使用Pol θ进行基因组保护的代价是通常会在修复位点处缺失或添加一些核苷酸。失活Pol θ经常增强细胞对DNA链断裂化学品和辐射的敏感性。由于一些同源重组缺陷癌症依赖Pol θ的生长,Pol θ的抑制剂可能在治疗此类肿瘤方面非常有用。
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.