Santocanale C, Diffley J F
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, UK.
Nature. 1998 Oct 8;395(6702):615-8. doi: 10.1038/27001.
DNA replication in eukaryotic cells initiates from many replication origins which fire throughout the S phase of the cell cycle in a predictable pattern: some origins fire early, others late. 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 and may aid cell survival under adverse conditions.
真核细胞中的DNA复制从多个复制起点起始，这些起点在细胞周期的S期以可预测的模式激活：一些起点早期激活，另一些晚期激活。关于在S期DNA复制起始与新合成DNA链的延伸如何协调，人们知之甚少。在这里我们表明，在芽殖酵母中，羟基脲可阻止复制叉从早期激活的起点前进，它也会抑制晚期起点的激活。这些晚期起点会在具备起始能力的复制前状态维持较长时间。对晚期起点激活的阻断是一个活跃的过程，在rad53和mec1检查点基因发生突变的酵母中存在缺陷，这表明对晚期起点激活的调控可能也是“S期内”检查点的一个重要组成部分，并且可能有助于细胞在不利条件下存活。
