Inhibition of eukaryotic DNA replication by geminin binding to Cdt1
Inhibition of eukaryotic DNA replication by geminin binding to Cdt1
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DOI：
10.1126/science.290.5500.2309
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发表时间：
2000-12-22
期刊：
影响因子：
56.9
通讯作者：
Dutta, A
中科院分区：
文献类型：
--
作者：
Wohlschlegel, JA;Dwyer, BT;Dutta, A
在所有真核生物中，细胞周期G（2）期复制起点的不适当放电受到细胞周期蛋白依赖性激酶的抑制。多细胞真核生物含有第二种假定的再复制抑制剂，称为Geminin，Geminin被认为可以阻断微型染色体维持（MCM）复合物与复制起点的结合，但这种抑制的机制尚不清楚。在这里，我们表明，双子相互作用紧密Cdt1，最近确定的复制起始因子所需的MCM加载。在无细胞DNA复制提取物中观察到的双生蛋白对DNA复制的抑制作用可通过加入过量Cdt1逆转。在正常细胞周期中，Cdt1仅存在于G（1）和S期，而双生蛋白存在于细胞周期的S和G（2）期。总之，这些结果表明，geminin抑制不适当的起源射击靶向Cdt1。
In all eukaryotic organisms, inappropriate firing of replication origins during the G(2) phase of the cell cycle is suppressed by cyclin-dependent kinases. Multicellular eukaryotes contain a second putative inhibitor of re-replication called geminin, Geminin is believed to block binding of the mini-chromosome maintenance (MCM) complex to origins of replication, but the mechanism of this inhibition is unclear. Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM Loading. The inhibition of DNA replication by geminin that is observed in cell-free DNA replication extracts is reversed by the addition of excess Cdt1. In the normal cell cycle, Cdt1 is present only in G(1) and S, whereas geminin is present in S and G(2) phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1.