Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex

Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex
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DOI:
10.1016/s0092-8674(00)81889-9
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发表时间:
1997-02-21
期刊:
影响因子:
64.5
通讯作者:
Bell, SP
Bell, SP
中科院分区:
生物学1区
文献类型:
--
作者:
Klemm, RD;Austin, RJ;Bell, SP

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起源识别复合物(ORC)是一个由六个蛋白质组成的装配体,它指定了S.啤酒。ORC的原产地识别需要ATP。在这里,我们证明了两个亚基,Orc 1 p和Orc 5 p,结合ATP和Orc 1 p也水解ATP。Orc 1 p对ATP的结合和水解都受到DNA序列特异性的调控。ATP与Orc 1 p的结合,而不是ATP水解,是ORC-起源相互作用的ATP依赖性的原因,表明ATP是将ORC锁定在起源DNA上的辅因子。这些数据表明,占用的Orc 1 p ATP结合位点具有深远的影响ORC功能和ATP水解的Orc 1 p有可能驱动ORC的不同功能状态之间的转换。
The Origin Recognition Complex (ORC) is a six-protein assembly that specifies the sites of DNA replication initiation in S. cerevisiae. Origin recognition by ORC requires ATP. Here, we demonstrate that two subunits, Orc1p and Orc5p, bind ATP and that Orc1p also hydrolyzes ATP. ATP binding and hydrolysis by Orc1p are both regulated by origin DNA in a sequence-specific manner. ATP binding to Orc1p, but not ATP hydrolysis, is responsible for the ATP dependence of the ORC-origin interaction, indicating that ATP is a cofactor that locks ORC on origin DNA. These data demonstrate that occupancy of the Orc1p ATP-binding site has a profound effect on ORC function and that ATP hydrolysis by Orc1p has the potential to drive transitions between different functional states of ORC.