A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage
A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage
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DOI：
10.1073/pnas.262669299
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发表时间：
2002-12-24
影响因子：
11.1
通讯作者：
Brown, GW
中科院分区：
文献类型：
--
作者：
Chang, M;Bellaoui, M;Brown, GW
我们对大约5000个可存活的酿酒酵母单倍体基因缺失突变体进行了系统筛选，并鉴定出103个基因，这些基因的缺失会导致对DNA损伤剂甲磺酸甲酯（MMS）敏感。总共鉴定出40个以前未被表征的烷基化损伤反应基因。与已知的受MMS诱导转录的基因集进行比较，发现与MMS抗性所需基因的重叠极少，这表明转录调控在对MMS损伤的反应中即使有作用，也是非常小的。根据对羟基脲、紫外线辐射和电离辐射的交叉敏感性对MMS反应基因进行聚类，揭示了一个对多种DNA损伤剂反应所需的基因的DNA损伤核心。特别重要的是，我们鉴定出了一个显示特定MMS反应的基因子集，它们仅在MMS存在时在S期进程中表现出缺陷。这些基因可能在复制叉与DNA损伤相遇时促进复制叉的稳定性或持续性。
We performed a systematic screen of the set of approximate to5,000 viable Saccharomyces cerevisiae haploid gene deletion mutants and have identified 103 genes whose deletion causes sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). In total, 40 previously uncharacterized alkylation damage response genes were identified. Comparison with the set of genes known to be transcriptionally induced in response to MMS revealed surprisingly little overlap with those required for MMS resistance, indicating that transcriptional regulation plays little, if any, role in the response to MMS damage. Clustering of the MMS response genes on the basis of their cross-sensitivities to hydroxyurea, UV radiation, and ionizing radiation revealed a DNA damage core of genes required for responses to a broad range of DNA-damaging agents. Of particular significance, we identified a subset of genes that show a specific MMS response, displaying defects in S phase progression only in the presence of MMS. These genes may promote replication fork stability or processivity during encounters between replication forks and DNA damage.