Beletskii A, Bhagwat A S
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13919-24. doi: 10.1073/pnas.93.24.13919.
Cytosines in single-stranded DNA deaminate to uracils at 140 times the rate for cytosines in double-stranded DNA. If resulting uracils are not replaced with cytosine, C to T mutations occur. These facts suggest that cellular processes such as transcription that create single-stranded DNA should promote C to T mutations. We tested this hypothesis with the Escherichia coli tac promoter and found that induction of transcription causes approximately 4-fold increase in the frequency of C to U or 5-methylcytosine to T deaminations in the nontranscribed strand. Excess mutations caused by C to U deaminations were reduced, but not eliminated, by uracil-DNA glycosylase. Similarly, mutations caused by 5-methylcytosine to T deaminations were only partially reduced by the very short-patch repair process in E.coli. These effects are unlikely to be caused by differential repair of the two strands, and our results suggest that all actively transcribed genes in E. coli should acquire more C to T mutations in the nontranscribed strand.
单链DNA中的胞嘧啶脱氨基形成尿嘧啶的速率是双链DNA中胞嘧啶的140倍。如果产生的尿嘧啶没有被胞嘧啶取代，就会发生C到T的突变。这些事实表明，诸如转录等产生单链DNA的细胞过程应该会促进C到T的突变。我们用大肠杆菌tac启动子检验了这一假设，发现转录的诱导会使非转录链中C到U或5-甲基胞嘧啶到T的脱氨基频率增加约4倍。尿嘧啶-DNA糖基化酶减少了由C到U脱氨基引起的过量突变，但并未消除。同样，大肠杆菌中极短补丁修复过程仅部分减少了由5-甲基胞嘧啶到T脱氨基引起的突变。这些效应不太可能是由两条链的差异修复引起的，我们的结果表明，大肠杆菌中所有活跃转录的基因在非转录链中应该会获得更多的C到T突变。
