Bousset K, Diffley J F
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
Genes Dev. 1998 Feb 15;12(4):480-90. doi: 10.1101/gad.12.4.480.
The Cdc7p protein kinase plays an essential, but undefined, role promoting S phase in the budding yeast, Saccharomyces cerevisiae. Previous experiments have shown that the essential function of Cdc7 is executed near the G1-S boundary; after Start but before the elongation phase of DNA replication. Origins of DNA replication fire throughout S phase in budding yeast. Therefore, the G1-S transition is a cell-cycle event that precedes, and is distinct from, the activation of individual origins. Consequently, we have asked whether Cdc7 is only required for S-phase entry or if it plays a role during S phase in origin firing. In this article, we show that partial loss of Cdc7 function results in slow progression through S phase rather than slow entry into S phase and that Cdc7 is still required for the timely completion of S phase after a block to elongation with hydroxyurea. This is because Cdc7 is still required for the activation of late-firing origins after the hydroxyurea block. These experiments show that, rather than acting as a global regulator of the G1-S transition, Cdc7 appears to play a more direct role in the firing of replication origins during S phase.
Cdc7p蛋白激酶在出芽酵母酿酒酵母中对促进S期起着至关重要但尚未明确的作用。先前的实验表明,Cdc7的基本功能在G1-S边界附近执行;在起始点之后但在DNA复制的延伸阶段之前。在出芽酵母中,DNA复制起点在整个S期都被激活。因此,G1-S转变是一个先于单个起点激活且与之不同的细胞周期事件。因此,我们探究了Cdc7是否仅在进入S期时是必需的,还是在S期起点激活过程中发挥作用。在本文中,我们表明Cdc7功能的部分丧失导致在S期进展缓慢,而非进入S期缓慢,并且在用羟基脲阻断延伸后,S期的及时完成仍需要Cdc7。这是因为在羟基脲阻断后,Cdc7对于晚期激活的起点的激活仍然是必需的。这些实验表明,Cdc7似乎并非作为G1-S转变的全局调节因子,而是在S期复制起点的激活中发挥更直接的作用。