Replication in hydroxyurea: It's a matter of time
Replication in hydroxyurea: It's a matter of time
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DOI：
10.1128/mcb.00719-07
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发表时间：
2007-09-01
影响因子：
5.3
通讯作者：
Raghuraman, M. K.
中科院分区：
文献类型：
--
作者：
Alvino, Gina M.;Collingwood, David;Raghuraman, M. K.
羟基脲 (HU) 是一种 DNA 复制抑制剂，会对复制的延伸期和起始期产生负面影响，并触发“S 期内检查点”。之前对出芽酵母的研究表明，在短暂暴露于 HU 的过程中，MEC1/RAD53 会阻止某些晚期 S 期起点的启动。在这项研究中，我们进行了微阵列实验，以追踪长期接触 HU 后所有来源的命运。我们发现，尽管时间框架非常不同，但在 HU 存在和不存在的情况下，DNA 合成（包括起始激活）的全基因组进展遵循相同的模式。我们没有发现任何证据表明存在排除晚期起源的特定效应。相反，HU 导致 S 期以慢动作进行；所有时间类别的起源都会受到影响，但它们变得活跃的顺序保持不变。我们提出了一个针对 HU 的检查点响应的修订模型，该模型解释了起源激活的时间程序的持续但缓慢的速度。
Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In this study, we have performed microarray experiments to follow the fate of all origins over an extended exposure to HU. We show that the genome-wide progression of DNA synthesis, including origin activation, follows the same pattern in the presence of HU as in its absence, although the time frames are very different. We find no evidence for a specific effect that excludes initiation from late origins. Rather, HU causes S phase to proceed in slow motion; all temporal classes of origins are affected, but the order in which they become active is maintained. We propose a revised model for the checkpoint response to HU that accounts for the continued but slowed pace of the temporal program of origin activation.