DNA polymerase β is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extracts
DNA polymerase β is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extracts
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DOI：
10.1093/emboj/20.23.6919
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发表时间：
2001-12-03
期刊：
影响因子：
11.4
通讯作者：
Dianov, GL
中科院分区：
文献类型：
--
作者：
Allinson, SL;Dianova, II;Dianov, GL
DNA中氧化碱基损伤的修复是一个协调的反应链，包括去除受损的碱基，在脱碱基糖残基处切割磷酸二酯骨架，掺入未受损的核苷酸和密封DNA链断裂。虽然哺乳动物细胞中受损碱基的去除主要由损伤特异性DNA糖基化酶启动，但几种裂解酶和DNA聚合酶可能有助于后期修复。DNA聚合酶β（Pol β）最近被认为是参与氧化性碱基损伤修复的主要聚合酶;然而，参与氧化性损伤修复的裂解酶的身份尚不清楚。我们研究了哺乳动物细胞提取物处理DNA底物的机制，该DNA底物在确定的位置含有单个8-氧代鸟嘌呤或5，6-二氢尿嘧啶。我们发现，当修复合成通过Pol β依赖性单核苷酸置换机制进行时，Pol β的5 '-脱氧核糖磷酸裂解酶活性对于两种损伤的修复都是必需的。
The repair of oxidative base lesions in DNA is a coordinated chain of reactions that includes removal of the damaged base, incision of the phosphodiester backbone at the abasic sugar residue, incorporation of an undamaged nucleotide and sealing of the DNA strand break. Although removal of a damaged base in mammalian cells is initiated primarily by a damage-specific DNA glycosylase, several lyases and DNA polymerases may contribute to the later stages of repair. DNA polymerase beta (Pol beta) was implicated recently as the major polymerase involved in repair of oxidative base lesions; however, the identity of the lyase participating in the repair of oxidative lesions is unclear. We studied the mechanism by which mammalian cell extracts process DNA substrates containing a single 8-oxoguanine or 5,6-dihydrouracil at a defined position. We find that, when repair synthesis proceeds through a Pol beta -dependent single nucleotide replacement mechanism, the 5'-deoxyribosephosphate lyase activity of Pol beta is essential for repair of both lesions.