Origin Licensing Requires ATP Binding and Hydrolysis by the MCM Replicative Helicase

被引：102

作者：

Coster, Gideon ^{[1
]}

Frigola, Jordi ^{[1
]}

Beuron, Fabienne ^{[2
]}

Morris, Edward P. ^{[2
]}

Diffley, John F. X. ^{[1
]}

机构：

[1] Imperial Canc Res Fund, Clare Hall Labs, Canc Res UK London Res Inst, S Mimms EN6 3LD, Herts, England

[2] Inst Canc Res, Div Struct Biol, London SW3 6JB, England

来源：

MOLECULAR CELL | 2014年 / 55卷 / 05期

基金：

欧洲研究理事会;

关键词：

DNA-REPLICATION; RECOGNITION COMPLEX; T-ANTIGEN; MOTIF; ACTIVATION; MECHANISMS; CDC6P; GINS;

D O I：

10.1016/j.molcel.2014.06.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. Assembly of these prereplicative complexes (pre-RCs) requires the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ORC, Cdc6, and MCM are members of the AAA+ family of ATPases, and pre-RC assembly requires ATP hydrolysis. Here we show that ORC and Cdc6 mutants defective in ATP hydrolysis are competent for origin licensing. However, ATP hydrolysis by Cdc6 is required to release nonproductive licensing intermediates. We show that ATP binding stabilizes the wildtype MCM hexamer. Moreover, by analyzing MCM containing mutant subunits, we show that ATP binding and hydrolysis by MCM are required for Cdt1 release and double hexamer formation. This work alters our view of how ATP is used by licensing factors to assemble pre-RCs.

引用

页码：666 / 677

页数：12

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