Human MutY: gene structure, protein functions and interactions, and role in carcinogenesis.
Human MutY: gene structure, protein functions and interactions, and role in carcinogenesis.
复制标题
人类 MutY：基因结构、蛋白质功能和相互作用以及在致癌作用中的作用。
DOI：
10.1007/s00018-003-3053-4
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Eshleman,JR
中科院分区：
文献类型：
--
作者：
Parker,AR;Eshleman,JR
基因组的忠实维护对个体和物种至关重要。氧化性DNA损伤，如8-氧代-7，8-二氢鸟嘌呤（8-oxoG），对基因组完整性构成重大威胁。8-在DNA复制过程中，OxoG可以与2′-脱氧胞苷5′-三磷酸或2′-脱氧腺苷三磷酸错配，形成C·8-oxoG和A·8-oxoG错配。人类MutY负责识别和去除A·8-oxoG错配中不适当插入的腺嘌呤。如果不修复，A·8-oxoG错配可能导致有害的C：G到A：T颠换。人MutY在复制后修复途径中发挥作用，并靶向新合成的DNA子链以去除腺嘌呤碱基。人MutY蛋白靶向线粒体和细胞核，并与增殖细胞核抗原、脱嘌呤/脱嘧啶核酸内切酶1、复制蛋白A和mutS同源物6蛋白相关。在癌症中检测到人类MutY基因的突变和人类MutY蛋白的缺陷活性。现在已经建立了缺陷A·8-oxoG修复与基因组8-oxoG水平增加之间的直接相关性。
Faithful maintenance of the genome is crucial to the individual and the species. Oxidative DNA damage, such as 8-oxo-7,8-dihydroguanine (8-oxoG), poses a major threat to genomic integrity. 8-OxoG can mispair with 2′-deoxycytidine 5′-triphosphate or with 2′-deoxyadenosine triphosphate during DNA replication, forming C•8-oxoG and A•8-oxoG mispairs. Human MutY is responsible for recognition and removal of the inappropriately inserted adenine in an A•8-oxoG mispair. If unrepaired, the A•8-oxoG mispairs can result in deleterious C:G to A:T transversions. Human MutY functions in a postreplication repair pathway and is targeted to the newly synthesized daughter strand of DNA for removal of the adenine base. The human MutY protein is targeted to both the mitochondria and the nucleus and associates with the proliferating cell nuclear antigen, apurinic/ apyrimidinic endonuclease 1, replication protein A and mutS homolog 6 proteins. Mutations in the humanMutYgene and defective activity of the human MutY protein have been detected in cancer. A direct correlation between defective A•8-oxoG repair and increased levels of genomic 8-oxoG has now been established.