A new member of the endonuclease III family of DNA repair enzymes that removes methylated purines from DNA
A new member of the endonuclease III family of DNA repair enzymes that removes methylated purines from DNA
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DOI：
10.1016/s0960-9822(99)80288-7
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发表时间：
1999-06-17
期刊：
影响因子：
9.2
通讯作者：
Cunningham, RP
中科院分区：
文献类型：
--
作者：
Begley, TJ;Haas, BJ;Cunningham, RP
DNA不断暴露于内源性和外源性的烷基化剂中，这些烷基化剂可以修饰DNA的碱基，导致在没有DNA修复的情况下发生突变[1,2]，烷基化损伤通过DNA糖基酶的作用被去除，从而启动碱基切除修复途径并保护基因组的序列信息[3-5]。我们发现了一类新的甲基嘌呤DNA糖基酶，命名为MpgII，它是DNA修复酶内切酶III家族的成员。我们从海洋热藻中表达并纯化了MpgII，发现该酶能从DNA中释放7-甲基鸟嘌呤和3-甲基腺嘌呤。我们克隆了海洋水蛭和风衣水蛭的MpgII基因，发现这两个基因都能恢复甲基甲磺酸盐（MMS）对缺乏烷基化碱基修复的大肠杆菌双突变体的抗性。在其他细菌和古细菌中也发现了类似的基因，并且似乎是这些生物体中编码甲基嘌呤DNA糖基酶活性的唯一基因。MpgII是DNA修复酶内切酶III家族的第五个成员，这表明内切酶III蛋白支架在进化过程中被修饰以识别和修复多种DNA损伤。(C) Elsevier Science Lid ISSN 0960-9822。
DNA is constantly exposed to endogenous and exogenous alkylating agents that can modify its bases, resulting in mutagenesis in the absence of DNA repair [1,2], Alkylation damage is removed by the action of DNA glycosylases, which initiate the base excision repair pathway and protect the sequence information of the genome [3-5], We have identified a new class of methylpurine DNA glycosylase, designated MpgII, that is a member of the endonuclease III family of DNA repair enzymes. We expressed and purified MpgII from Thermotoga maritima and found that the enzyme releases both 7-methylguanine and 3-methyladenine from DNA. We cloned the MpgII genes from T. maritima and from Aquifex aeolicus and found that both genes could restore methylmethanesulfonate (MMS) resistance to Escherichia coli alkA tagA double mutants, which are deficient in the repair of alkylated bases. Analogous genes are found in other Bacteria and Archaea and appear to be the only genes coding for methylpurine DNA glycosylase activity in these organisms. MpgII is the fifth member of the endonuclease III family of DNA repair enzymes, suggesting that the endonuclease III protein scaffold has been modified during evolution to recognize and repair a variety of DNA damage. (C) Elsevier Science Lid ISSN 0960-9822.