Fromme J Christopher, Verdine Gregory L
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
EMBO J. 2003 Jul 1;22(13):3461-71. doi: 10.1093/emboj/cdg311.
Nearly all cells express proteins that confer resistance to the mutagenic effects of oxidative DNA damage. The primary defense against the toxicity of oxidative nucleobase lesions in DNA is the base-excision repair (BER) pathway. Endonuclease III (EndoIII) is a [4Fe-4S] cluster-containing DNA glycosylase with repair activity specific for oxidized pyrimidine lesions in duplex DNA. We have determined the crystal structure of a trapped intermediate that represents EndoIII frozen in the act of repairing DNA. The structure of the protein-DNA complex provides insight into the ability of EndoIII to recognize and repair a diverse array of oxidatively damaged bases. This structure also suggests a rationale for the frequent occurrence in certain human cancers of a specific mutation in the related DNA repair protein MYH.
几乎所有细胞都表达能抵抗氧化性DNA损伤诱变效应的蛋白质。针对DNA中氧化性核碱基损伤毒性的主要防御机制是碱基切除修复(BER)途径。核酸内切酶III(EndoIII)是一种含[4Fe-4S]簇的DNA糖基化酶,对双链DNA中氧化的嘧啶损伤具有特异性修复活性。我们已经确定了一种捕获中间体的晶体结构,该中间体代表处于修复DNA过程中的EndoIII。蛋白质-DNA复合物的结构有助于深入了解EndoIII识别和修复多种氧化性损伤碱基的能力。这种结构还为相关DNA修复蛋白MYH中特定突变在某些人类癌症中频繁出现提供了一种解释。