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.

Center for Chromosome Stability and Center for Healthy Aging Department of Cellular and Molecular Medicine University of Copenhagen Copenhagen N Denmark

National Centre for Biomolecular Research and Department of Biology Masaryk University and St Anne's University Hospital Brno Czech Republic

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

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RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome

Quantity and quality of minichromosome maintenance protein complexes couple replication licensing to genome integrity

Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase