PMC:1140370 / 35969-37852 JSONTXT

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A crucial question is how these double hexameric helicase complexes are generated and turn into active helicases at the origins. This process would involve melting of duplex DNA, which may be facilitated by binding of preRC components in the context of proper chromatin structures, or by other unwinding factors including a topoisomerase or a newly identified Mcm8 helicase (34–36). It may also require association of fork-assisting proteins such as Cdc45 (37,38) as well as phosphorylation events by Cdk and Cdc7 kinases (39,40). One unexpected finding of this study is low helicase activity of Mcm4/6/7 on GC-rich duplex DNA. This, in conjunction with the low processivity of Mcm4/6/7 helicase, strongly indicates that the replicative helicase at the replication forks would require more than Mcm4/6/7 complex. During the processive unwinding of duplex DNA replication forks, Mcm4/6/7 may be further stimulated by interaction with other proteins, including remaining Mcm subunits, Cdc45 (37,38), GINS (41,42), DNA polymerase subunits (43), Mcm8 (35,36), etc. to become a truly processive and potent helicase capable of replicating the entire 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