PATHWAY CORRECTING DNA-REPLICATION ERRORS IN SACCHAROMYCES-CEREVISIAE
PATHWAY CORRECTING DNA-REPLICATION ERRORS IN SACCHAROMYCES-CEREVISIAE
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DOI：
10.1002/j.1460-2075.1993.tb05790.x
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发表时间：
1993-04-01
期刊：
影响因子：
11.4
通讯作者：
SUGINO, A
中科院分区：
文献类型：
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作者：
MORRISON, A;JOHNSON, AL;SUGINO, A
酿酒酵母POL3 DNA聚合酶（δ）预测的3'→5'核酸外切酶活性位点残基的突变，或者PMS1错配修复基因的缺失，在靠近一个确定的复制起点插入的URA3报告基因处测量时，相对于野生型，自发突变率分别约为130和41。POL3核酸外切酶缺陷型突变体pol3 - 01在URA3中产生了大多数类型的单碱基突变，表明其具有广泛的特异性，通常与PMS1系统相对应。pol3 - 01 pms1单倍体细胞在分裂几次后停止生长，没有独特的末端细胞形态。一个pol3 - 01/pol3 - 01 pms1/pms1二倍体是有活力的，并且显示出估计的URA3相对突变率为2×10⁴，我们计算得出这在单倍体中是灾难性的高。pol3 - 01和pms1的相对突变率之间是相乘关系，表明是串联作用。PMFS1转录本显示出与包括POL3在内的一组DNA复制基因相同的细胞周期周期性，这表明PMS1与这些基因是共同调控的。我们提出POL3的3'→5'核酸外切酶和PMS1错配修复系统在一条类似于大肠杆菌中dnaQ→mutHLS的DNA复制错误校正途径的共同途径上起作用。
Mutation of predicted 3'--> 5' exonuclease active site residues of Saccharomyces cerevisiae POL3 DNA polymerase (delta) or deletion of the PMS1 mismatch repair gene lead to relative (to wild type) spontaneous mutation rates of approximately 130 and 41, respectively, measured at a URA3 reporter gene inserted near to a defined replication origin. The POL3 exonuclease-deficient mutant pol3-01 generated most classes of single base mutation in URA3, indicating a broad specificity that generally corresponds to that of the PMS1 system. pol3-01 pms1 haploid cells ceased growth after a few divisions with no unique terminal cell morphology. A pol3-01/pol3-01 pms1/pms1 diploid was viable and displayed an estimated URA3 relative mutation rate of 2 X 10(4), which we calculate to be catastrophically high in a haploid. The relationship between the relative mutation rates of pol3-01 and pms1 was multiplicative, indicating action in series. The PMFS1 transcript showed the same cell cycle periodicity as those of a set of DNA replication genes that includes POL3, suggesting PMS1 is co-regulated with these genes. We propose that the POL3 3'--> 5' exonuclease and the PMS1 mismatch repair system act on a common pathway analogous to the dnaQ --> mutHLS pathway of DNA replication error correction in Escherichia coli.