Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

• Published in: Oncotarget Vol. 6; no. 38; pp. 40464 - 40479
• Main Authors: Kliszczak, Maciej, Sedlackova, Hana, Pitchai, Ganesha P, Streicher, Werner W, Krejci, Lumir, Hickson, Ian D
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 01.12.2015
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Blotting, Western; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Proliferation; Chickens - genetics; Chromatin - genetics; DNA Replication; Flow Cytometry; Humans; Immunoenzyme Techniques; Immunoprecipitation; Minichromosome Maintenance Complex Component 2 - genetics; Minichromosome Maintenance Complex Component 2 - metabolism; Minichromosome Maintenance Complex Component 7 - genetics; Minichromosome Maintenance Complex Component 7 - metabolism; Minichromosome Maintenance Proteins - genetics; Minichromosome Maintenance Proteins - metabolism; Molecular Sequence Data; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Protein Interaction Domains and Motifs; Real-Time Polymerase Chain Reaction; RecQ Helicases - genetics; RecQ Helicases - metabolism; Replication Origin - genetics; Research Paper: Chromosome; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Sequence Homology, Amino Acid; Surface Plasmon Resonance; Tumor Cells, Cultured; minichromosome maintenance proteins; DNA replication; Chromosome Section; RecQ helicases
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.6342

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.