Suzuki Tetsuya, Yamamoto Kazuo, Harashima Hideyoshi, Kamiya Hiroyuki
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
DNA Repair (Amst). 2008 Jan 1;7(1):88-94. doi: 10.1016/j.dnarep.2007.08.003. Epub 2007 Sep 17.
To examine whether base excision repair suppresses mutations induced by oxidized deoxyribonucleotide 5'-triphosphates in the nucleotide pool, 8-hydroxy-dGTP (8-OH-dGTP) and 2-hydroxy-dATP were introduced into Escherichia coli strains deficient in endonucleases III (Nth) and VIII (Nei) and MutY, and mutations in the chromosomal rpoB gene were analyzed. The spontaneous rpoB mutant frequency was also examined in mutT/nth and mutT/nei strains, to assess the influence on the mutations induced by the endogenous 8-OH-dGTP accumulated in the mutT mutant. The mutations induced by exogenous 2-hydroxy-dATP were similar in all of the strains tested. Exogenous 8-OH-dGTP increased the rpoB mutant frequency more efficiently in the nth strain than that in the wild-type strain. The spontaneous mutant frequency in the mutT/nth strain was 2-fold higher than that in the mutT strain. These results suggest that E. coli endonuclease III also acts as a defense against the mutations caused by 8-OH-dGTP in the nucleotide pool.
为了研究碱基切除修复是否能抑制核苷酸池中氧化脱氧核糖核苷酸5'-三磷酸诱导的突变，将8-羟基-dGTP（8-OH-dGTP）和2-羟基-dATP导入缺乏核酸内切酶III（Nth）、核酸内切酶VIII（Nei）和MutY的大肠杆菌菌株中，并分析染色体rpoB基因中的突变。还检测了mutT/nth和mutT/nei菌株中rpoB基因的自发突变频率，以评估对mutT突变体中积累的内源性8-OH-dGTP诱导的突变的影响。在所有测试菌株中，外源性2-羟基-dATP诱导的突变相似。外源性8-OH-dGTP在nth菌株中比在野生型菌株中更有效地增加了rpoB突变频率。mutT/nth菌株中的自发突变频率比mutT菌株中的高2倍。这些结果表明，大肠杆菌核酸内切酶III也可作为抵御核苷酸池中8-OH-dGTP引起的突变的一种防御机制。
