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EMBO J
2009 Oct 07;2819:3005-14. doi: 10.1038/emboj.2009.235.
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MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication.
Xu X
,
Rochette PJ
,
Feyissa EA
,
Su TV
,
Liu Y
.
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Mutations in RECQ4, a member of the RecQ family of DNA helicases, have been linked to the progeroid disease Rothmund-Thomson Syndrome. Attempts to understand the complex phenotypes observed in recq4-deficient cells suggest a potential involvement in DNA repair and replication, yet the molecular basis of the function of RECQ4 in these processes remains unknown. Here, we report the identification of a highly purified chromatin-bound RECQ4 complex from human cell extracts. We found that essential replisome factors MCM10, MCM2-7 helicase, CDC45 and GINS are the primary interaction partner proteins of human RECQ4. Importantly, complex formation and the association of RECQ4 with the replication origin are cell-cycle regulated. Furthermore, we show that MCM10 is essential for the integrity of the RECQ4-MCM replicative helicase complex. MCM10 interacts directly with RECQ4 and regulates its DNA unwinding activity, and that this interaction may be modulated by cyclin-dependent kinase phosphorylation. Thus, these studies show that RECQ4 is an integral component of the MCM replicative helicase complex participating in DNA replication in human cells.
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