Altered fidelity of mitotic chromosome transmission in cell cycle mutants of S. cerevisiae.
Altered fidelity of mitotic chromosome transmission in cell cycle mutants of S. cerevisiae.
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DOI：
10.1093/genetics/110.3.381
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发表时间：
1985-07
期刊：
影响因子：
3.3
通讯作者：
L. Hartwell;David M. Smith
中科院分区：
文献类型：
--
作者：
L. Hartwell;David M. Smith
14个温度敏感突变体中有13个缺乏有丝分裂染色体传递的连续步骤（cdc 2，4，5，6，7，8，9，13，14，15，16，17和20）从纺锤体极体分离到核分裂后期，染色体丢失的频率急剧增加，或有丝分裂重组时，他们生长在其最高允许温度。染色体丢失和/或重组的增加可能是由于功能性基因产物的缺陷，而不是突变基因产物的异常功能，因为对于该表型，突变等位基因对于野生型等位基因是隐性的，只有一个例外。这一结果的普遍性表明，在几乎任何阶段的染色体复制或分离的延迟导致有丝分裂染色体传递的保真度降低。相反，在细胞周期的控制步骤（cdc 28）、胞质分裂（cdc 3）或蛋白质合成（ils 1）中有缺陷的温度敏感突变体没有表现出增加的重组或染色体丢失。根据以前的结果与突变体和DNA损伤剂在各种生物体中，我们认为，诱导有丝分裂重组在某些突变体是由于修复途径的作用后，缺口或缺口留在DNA。这种解释得到了以下事实的支持：诱导的重组依赖于RAD 52基因产物，作为重组DNA修复途径中的重要组分。因此，其缺陷导致诱导重组的基因产物是在DNA代谢中起作用的蛋白质的强有力的候选者。在诱导重组的突变体中，已知在DNA复制的某些方面有缺陷的突变体（cdc 2、6、8、9）以及在有丝分裂周期的G2（cdc 13和17）和M（cdc 5和14）期有缺陷的一些突变体。我们认为，DNA代谢的特殊方面可能发生在G2和M，以准备染色体适当的分离。
Thirteen of 14 temperature-sensitive mutants deficient in successive steps of mitotic chromosome transmission (cdc2, 4, 5, 6, 7, 8, 9, 13, 14, 15, 16, 17 and 20) from spindle pole body separation to a late stage of nuclear division exhibited a dramatic increase in the frequency of chromosome loss and/or mitotic recombination when they were grown at their maximum permissive temperatures. The increase in chromosome loss and/or recombination is likely to be due to the deficiency of functional gene product rather than to an aberrant function of the mutant gene product since the mutant alleles are, with one exception, recessive to the wild-type allele for this phenotype. The generality of this result suggests that a delay in almost any stage of chromosome replication or segregation leads to a decrease in the fidelity of mitotic chromosome transmission. In contrast, temperature-sensitive mutants defective in the control step of the cell cycle (cdc28), in cytokinesis (cdc3) or in protein synthesis (ils1) did not exhibit increased recombination or chromosome loss.--Based upon previous results with mutants and DNA-damaging agents in a variety of organisms, we suggest that the induction of mitotic recombination in certain mutants is due to the action of a repair pathway upon nicks or gaps left in the DNA. This interpretation is supported by the fact that the induced recombination is dependent upon the RAD52 gene product, as essential component in the recombinogenic DNA repair pathway. Gene products whose deficiency leads to induced recombination are, therefore, strong candidates for proteins that function in DNA metabolism. Among the mutants that induce recombination are those known to be defective in some aspect of DNA replication (cdc2, 6, 8, 9) as well as some mutants defective in the G2 (cdc13 and 17) and M (cdc5 and 14) phases of the mitotic cycle. We suggest that special aspects of DNA metabolism may be occurring in G2 and M in order to prepare the chromosomes for proper segregation.