A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication
A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication
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DOI：
10.1038/27001
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发表时间：
1998-10-08
期刊：
影响因子：
64.8
通讯作者：
Diffley, JFX
中科院分区：
文献类型：
--
作者：
Santocanale, C;Diffley, JFX
真核细胞中的 DNA 复制从许多复制起点 (1) 开始，这些复制起点以可预测的模式贯穿细胞周期的 S 期：有些起点较早，有些较晚 (2)。关于 S 期 DNA 复制的启动和新合成的 DNA 链的延伸是如何协调的，人们知之甚少。在这里，我们发现，在出芽酵母中，羟基脲可以阻止复制叉从早期激发起源的进展，也抑制晚期起源的激发。这些晚期起源在较长时间内维持在有启动能力的复制前状态。阻止晚期起源放电是一个活跃的过程，并且在 rad53 和 mec1 检查点基因突变的酵母中存在缺陷，表明晚期起源放电的调节也可能是“S 期内”检查点的重要组成部分 (3)，并且可能有助于细胞在不利条件下生存。
DNA replication in eukaryotic cells initiates from many replication origins(1) which fire throughout the S phase of the cell cycle in a predictable pattern: some origins fire early, others late(2). Little is known about how the initiation of DNA replication and the elongation of newly synthesized DNA strands are coordinated during S phase. Here we show that, in budding yeast, hydroxyurea, which blocks the progression of replication forks from early-firing origins, also inhibits the firing of late origins. These late origins are maintained in the initiation-competent prereplicative state for extended periods. The block to late origin firing is an active process and is defective in yeast with mutations in the rad53 and mec1 checkpoint genes, indicating that regulation of late origin firing may also be an important component of the 'intra-S-phase' checkpoint(3) and may aid cell survival under adverse conditions.