title: Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells.
abstract: DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kliszczak
authors.affiliation: National Centre for Biomolecular Research and Department of Biology, Masaryk University, and St Anne's University Hospital, Brno, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Sedlackova
authors.affiliation: Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Ganesha P
authors.initials: GP
authors.lastname: Pitchai
authors.affiliation: Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.|Present address: Novozymes A/S, Bagsvaerd, Denmark.
authors.forename: Werner W
authors.initials: WW
authors.lastname: Streicher
authors.affiliation: National Centre for Biomolecular Research and Department of Biology, Masaryk University, and St Anne's University Hospital, Brno, Czech Republic.
authors.forename: Lumir
authors.initials: L
authors.lastname: Krejci
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hickson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002645:Chickens / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D004261:DNA Replication; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D064111:Minichromosome Maintenance Complex Component 2 / Q000235:genetics / Q000378:metabolism; D064168:Minichromosome Maintenance Complex Component 7 / Q000235:genetics / Q000378:metabolism; D064110:Minichromosome Maintenance Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054730:Protein Interaction Domains and Motifs; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D018741:Replication Origin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D014407:Tumor Cells, Cultured
chemical_list: D002843:Chromatin; C489613:MCM10 protein, human; D012333:RNA, Messenger; 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
keywords: Chromosome Section; DNA replication; RecQ helicases; minichromosome maintenance proteins