Oncotarget

Research Papers: Chromosome:

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

Maciej Kliszczak _, Hana Sedlackova, Ganesha P. Pitchai, Werner W. Streicher, Lumir Krejci and Ian D. Hickson

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Oncotarget. 2015; 6:40464-40479. https://doi.org/10.18632/oncotarget.6342

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Abstract

Maciej Kliszczak1, Hana Sedlackova2, Ganesha P. Pitchai3, Werner W. Streicher3,4, Lumir Krejci2 and Ian D. Hickson1

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

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

3 Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark

4 Present address: Novozymes A/S, 2880 Bagsvaerd, Denmark

Correspondence to:

Ian D. Hickson, email:

Keywords: DNA replication, RecQ helicases, minichromosome maintenance proteins, Chromosome Section

Received: November 09, 2015 Accepted: November 10, 2015 Published: November 17, 2015

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.


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