title: MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication.
abstract: 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.
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Rochette
authors.forename: Eminet A
authors.initials: EA
authors.lastname: Feyissa
authors.forename: Tina V
authors.initials: TV
authors.lastname: Su
authors.forename: Yilun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D064168:Minichromosome Maintenance Complex Component 7; D064110:Minichromosome Maintenance Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D053484:RecQ Helicases / Q000302:isolation & purification / Q000378:metabolism*; D018741:Replication Origin
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C489613:MCM10 protein, human; D009687:Nuclear Proteins; D004247:DNA; C506731:RECQL4 protein, human; C084859:MCM2 protein, human; C101624:MCM7 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D064168:Minichromosome Maintenance Complex Component 7; D064110:Minichromosome Maintenance Proteins; D053484:RecQ Helicases
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