Mrc1 Marks Early-Firing Origins and Coordinates Timing and Efficiency of Initiation in Fission Yeast
Mrc1 Marks Early-Firing Origins and Coordinates Timing and Efficiency of Initiation in Fission Yeast
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DOI：
10.1128/mcb.01239-10
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发表时间：
2011-06-01
影响因子：
5.3
通讯作者：
Masai, Hisao
中科院分区：
文献类型：
--
作者：
Hayano, Motoshi;Kanoh, Yutaka;Masai, Hisao
真核生物染色体上的早发和迟发起源是如何被选择的，这在很大程度上是未知的。在这里，我们表明，Mrc1，稳定停滞的复制叉所需的保守因子，选择性地结合到早期发射的起源在一种独立的方式Cdc45和HSK 1激酶的裂殖酵母裂殖酵母粟酒裂殖酵母。在mrc1 Delta细胞中（在一定程度上也在swi1 Delta细胞中），激发的效率受到刺激，并且在通常由Mrc1约束的那些起源处，其定时选择性地提前。相反，不被Mrc1结合的晚期或低效起源在mrc1 δ细胞中不被激活。增强的射击和早熟Cdc45加载在Mrc1结合的早期射击的起源没有观察到在检查点突变的mrc1，这表明非检查点功能参与维持正常程序的早期射击的起源。我们建议，prefiring结合的Mrc1是一个重要的标志，早期发射的起源是早熟激活的情况下，这种蛋白质。
How early-and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing origins in a manner independent of Cdc45 and Hsk1 kinase in the fission yeast Schizosaccharomyces pombe. In mrc1 Delta cells (and in swi1 Delta cells to some extent), efficiency of firing is stimulated, and its timing is advanced selectively at those origins that are normally bound by Mrc1. In contrast, the late or inefficient origins which are not bound by Mrc1 are not activated in mrc1 Delta cells. The enhanced firing and precocious Cdc45 loading at Mrc1-bound early-firing origins are not observed in a checkpoint mutant of mrc1, suggesting that non-checkpoint function is involved in maintaining the normal program of early-firing origins. We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein.