Kaufman E R
Center for Genetics, University of Illinois College of Medicine at Chicago, IL 60612.
Mutat Res. 1988 Jul-Aug;200(1-2):149-55. doi: 10.1016/0027-5107(88)90077-2.
The effects of deoxyribonucleoside triphosphate (dNTP) pool imbalance on the induction of mutations and sister-chromatid exchanges (SCEs) by 5-bromo-2'-deoxyuridine (BrdUrd) in mammalian cells is reviewed. The INC BrdUrd mutagenesis protocol involves the incorporation of BrdUrd into DNA under conditions of specific dNTP pool imbalance, while the REP BrdUrd mutagenesis protocol involves the replication of 5-bromouracil (BrUra)-substituted DNA in the presence of specific (but different) dNTP pool imbalance. Biochemical and genetic analyses of both the INC and REP mutagenesis protocols provided evidence that (1) INC mutagenesis resulted from errors of incorporation due to the mispairing of BrdUTP with a guanine residue in replicating DNA leading to GC to AT transitions and (2) REP mutagenesis resulted from errors of replication due to the mispairing of dGTP with a BrUra residue in replicating DNA leading to AT to GC transitions. Further analyses involving different cell lines has led to an hypothesis describing the role of mismatch repair in the induction of mutations and SCEs.
本文综述了脱氧核糖核苷三磷酸（dNTP）库失衡对5-溴-2'-脱氧尿苷（BrdUrd）在哺乳动物细胞中诱导突变和姐妹染色单体交换（SCE）的影响。INC BrdUrd诱变方案涉及在特定dNTP库失衡条件下将BrdUrd掺入DNA，而REP BrdUrd诱变方案涉及在特定（但不同）dNTP库失衡存在下复制5-溴尿嘧啶（BrUra）取代的DNA。对INC和REP诱变方案的生化和遗传分析提供了证据，表明（1）INC诱变是由于在复制DNA中BrdUTP与鸟嘌呤残基错配导致的掺入错误，从而导致GC到AT的转换；（2）REP诱变是由于在复制DNA中dGTP与BrUra残基错配导致的复制错误，从而导致AT到GC的转换。涉及不同细胞系的进一步分析得出了一个假设，描述了错配修复在诱导突变和SCE中的作用。
