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DNA复制和损伤检查点通路通过抑制Crt1抑制器来诱导转录
1Howard Hughes Medical Institute, Verna & Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA.
Cell
|September 19, 1998
概括
酵母CRT1基因作为DNA损伤反应调节器,在复制应激过程中防止细胞死亡. 它通过结合DNA来控制基因表达,并被DNA损伤所抑制,形成一个保存的负反循环.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- DNA损伤和复制检查点路径对于保持基因组稳定性至关重要.
- 了解这些通路的调节机制对于理解细胞对压力的反应至关重要.
研究的目的:
- 为了确定酵母DNA损伤和复制检查点路径中的关键效应因子.
- 阐明CRT1基因在调节受损诱导基因和细胞活力的作用.
主要方法:
- 酵母CRT1基因的基因识别和表征.
- 对蛋白质相互作用的分析,包括DNA结合和抑制剂Ssn6和Tup1.1的招募.
- 评估基因表达的变化,以应对DNA损伤和复制压力.
- 在各种压力条件下评估细胞活力,包括mec1和rad53无基因突变.
主要成果:
- CRT1编码了一种DNA结合蛋白,通过招募Ssn6和Tup1来作为受损诱导基因的抑制剂.
- 抑制CRT1规律对复制性应激期间的细胞存活至关重要,并抑制mec1和rad53突变的致死性.
- CRT1在DNA损伤时经历过酸化,导致其与DNA分离和转录诱导.
- CRT1是自我调节的,并由DNA损伤引起,建立一个负反循环.
结论:
- CRT1是DNA损伤和复制检查点途径中的关键效应因子,对应激下细胞活力至关重要.
- 涉及CRT1的自我调节负反机制有助于在消除压力后及时抑制损伤诱导的基因.
- 作为对DNA损伤的反应,抑制自身调节抑制剂的已识别的机制在 prokaryotes 和 eukaryotes 中被进化保存.
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