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

Authors: Kliszczak, Maciej; Sedlackova, Hana; Pitchai, Ganesha P; Streicher, Werner W; Krejci, Lumir; Hickson, Ian D;

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.

Keywords

DNA Replication, Osteosarcoma, Minichromosome Maintenance Proteins, Blotting, Western, Molecular Sequence Data, Apoptosis, Bone Neoplasms, Minichromosome Maintenance Complex Component 2, Flow Cytometry, Minichromosome Maintenance Complex Component 7, Chromatin, Immunoenzyme Techniques, Animals, Humans, Immunoprecipitation, Protein Interaction Domains and Motifs, Amino Acid Sequence, RNA, Messenger, Chickens, Cell Proliferation

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    30
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
30
Top 10%
Average
Top 10%
Green
gold