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      Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.

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          Abstract

          The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs). Mcm2-7 forms the core of the replicative DNA helicase, which is inactive in the pre-RC. The loading of Mcm2-7 onto DNA requires the origin recognition complex (ORC), Cdc6, and Cdt1, and depends on ATP. We have reconstituted Mcm2-7 loading with purified budding yeast proteins. Using biochemical approaches and electron microscopy, we show that single heptamers of Cdt1*Mcm2-7 are loaded cooperatively and result in association of stable, head-to-head Mcm2-7 double hexamers connected via their N-terminal rings. DNA runs through a central channel in the double hexamer, and, once loaded, Mcm2-7 can slide passively along double-stranded DNA. Our work has significant implications for understanding how eukaryotic DNA replication origins are chosen and licensed, how replisomes assemble during initiation, and how unwinding occurs during DNA replication.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          1097-4172
          0092-8674
          Nov 13 2009
          : 139
          : 4
          Affiliations
          [1 ] Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, UK.
          Article
          S0092-8674(09)01303-8 NIHMS155645
          10.1016/j.cell.2009.10.015
          2804858
          19896182
          80fe73df-fb62-49bd-89bb-00d6611d03bb
          History

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