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Series GSE248981 Query DataSets for GSE248981
Status Public on Mar 28, 2024
Title DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.
Organism Homo sapiens
Experiment type Other
Summary In eukaryotes, CDC7 kinase is crucial for DNA replication initiation and has been involved in fork processing and replication stress response. Human CDC7 requires the binding of either one of two regulatory subunits, DBF4 and DRF1, for its activity. However, it is unclear whether the two regulatory subunits target CDC7 to a specific set of substrates, thus having different biological functions, or if they act redundantly. Using genome editing technology, we generated an isogenic set of cell lines deficient in either one of the two CDC7-activating subunits: these cells are viable but present signs of genomic instability, indicating that both DBF4 and DRF1 can independently support CDC7 for bulk DNA replication. Nonetheless, DBF4-deficient cells show altered replication efficiency, including partial deficiency in MCM helicase phosphorylation and alterations in the replication timing of discrete genomic regions. Notably, we find that CDC7 function at replication forks is entirely dependent on DBF4 and not DRF1. Thus, DBF4 is the primary regulator of CDC7 activity, likely mediating most of its functions in unperturbed DNA replication and during replication fork processing upon replication interference.
Overall design nascent-DNA from early S-phase versus nascent-DNA from late S-phase
Contributor(s) Göder A, Maric C, Cadoret J, Santocanale C
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Submission date Nov 29, 2023
Last update date Mar 29, 2024
Contact name Chrystelle Maric
Phone 0157278074
Organization name CNRS
Department UMR7592 Institut Jacques-Monod
Lab Pathology of DNA replication
Street address 15 rue Hélène Brion
ZIP/Postal code 75205
Country France
Platforms (1)
GPL10123 Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version)
Samples (12)
GSM7924256 MCF10A DMSO treated Replicate 1
GSM7924257 MCF10A DMSO treated Replicate 2
GSM7924258 MCF10A DMSO treated Replicate 3
BioProject PRJNA1046531

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE248981_MCF10A_DMSO_vs_DBF4-deficient-cells.bed.gz 2.1 Kb (ftp)(http) BED
GSE248981_MCF10A_DMSO_vs_XL413.bed.gz 3.6 Kb (ftp)(http) BED
GSE248981_RAW.tar 625.6 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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