Tajiri T, Maki H, Sekiguchi M
Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Mutat Res. 1995 May;336(3):257-67. doi: 10.1016/0921-8777(94)00062-b.
8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is a potent mutagenic substrate for DNA synthesis. The accumulation of 8-oxo-dGTP in the nucleotide pool induces G:C-->T:A transversion as well as A:T-->C:G transversion, and Escherichia coli cells possess mechanisms for preventing such mutations. The mutT gene product specifically hydrolyzes 8-oxo-dGTP to the monophosphate form while the mutM and the mutY gene products function to correct mispairs caused by incorporation of 8-oxoguanine into DNA. From analyses of forward mutations induced in cells lacking 8-oxo-dGTPase (MutT protein) and/or repair enzymes that suppress mutations caused by 8-oxoguanine in DNA (MutM and MutY proteins), cooperative functions of these proteins in control of the spontaneous mutagenesis became evident. In mutator strains lacking MutT and/or MutM proteins, 8-oxoguanine of DNA increased to a concentration expected from the increased rate of mutation.
8-氧代-dGTP（8-氧代-7,8-二氢脱氧鸟苷三磷酸）是DNA合成的一种强效诱变底物。核苷酸池中8-氧代-dGTP的积累会诱导G:C→T:A颠换以及A:T→C:G颠换，而大肠杆菌细胞拥有防止此类突变的机制。mutT基因产物可将8-氧代-dGTP特异性水解为单磷酸形式，而mutM和mutY基因产物的功能是纠正由8-氧代鸟嘌呤掺入DNA所导致的错配。通过对缺乏8-氧代-dGTP酶（MutT蛋白）和/或抑制DNA中8-氧代鸟嘌呤引起的突变的修复酶（MutM和MutY蛋白）的细胞中诱导的正向突变进行分析，这些蛋白在控制自发诱变中的协同功能变得明显。在缺乏MutT和/或MutM蛋白的突变菌株中，DNA中的8-氧代鸟嘌呤增加到了与突变率增加预期相符的浓度。
