The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor
The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor
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DOI：
10.1016/s0092-8674(00)81601-3
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发表时间：
1998-09-04
期刊：
影响因子：
64.5
通讯作者：
Elledge, SJ
中科院分区：
文献类型：
--
作者：
Huang, MX;Zhou, Z;Elledge, SJ
我们已经确定了酵母CRT1基因作为DNA损伤和复制检查点途径的效应子。CRT1编码一种DNA结合蛋白，其将一般阻遏物Ssn6和Tup1募集到损伤诱导基因的启动子。Crt1调节子的去阻遏抑制了mec1和rad53无效等位基因的致死性，并且对于复制应激期间的细胞活力是必需的。作为对DNA损伤和复制阻断的反应，Crt1变得过度磷酸化，不再结合DNA，导致转录诱导。CRT1是自动调节的，本身由DNA损伤诱导，表明存在负反馈途径，有助于在消除损伤后恢复到受抑制状态。抑制自身调节阻遏物对DNA损伤的反应是贯穿原核和真核进化的保守策略。
We have identified the yeast CRT1 gene as an effector of the DNA damage and replication checkpoint pathway. CRT1 encodes a DNA-binding protein that recruits the general repressors Ssn6 and Tupl to the promoters of damage-inducible genes. Derepression of the Crt1 regulon suppresses the lethality of mec1 and rad53 null alleles and is essential for cell viability during replicative stress. In response to DNA damage and replication blocks, Crt1 becomes hyperphosphorylated and no longer binds DNA, resulting in transcriptional induction. CRT1 is autoregulated and is itself induced by DNA damage, indicating the existence of a negative feedback pathway that facilitates return to the repressed state after elimination of damage. The inhibition of an autoregulatory repressor in response to DNA damage is a strategy conserved throughout prokaryotic and eukaryotic evolution.