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| 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
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| 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.
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| Overall design |
nascent-DNA from early S-phase versus nascent-DNA from late S-phase
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| Contributor(s) |
Göder A, Maric C, Cadoret J, Santocanale C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 29, 2023 |
| Last update date |
Mar 29, 2024 |
| Contact name |
Chrystelle Maric |
| E-mail(s) |
chrystelle.maric@ijm.fr
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| Phone |
0157278074
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| Organization name |
CNRS
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| Department |
UMR7592 Institut Jacques-Monod
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| Lab |
Pathology of DNA replication
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| Street address |
15 rue Hélène Brion
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| City |
PARIS |
| ZIP/Postal code |
75205 |
| Country |
France |
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| Platforms (1) |
| GPL10123 |
Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1046531 |
| 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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