Target type: cellularcomponent
A heterodimeric protein complex required for the activation of DNA replication origins; comprises a catalytic subunit and a regulatory subunit (in Saccharomyces, Cdc7p and Dbf4p, respectively); complexes identified in other species generally contain proteins related to the Saccharomyces proteins. [PMID:12045100]
The Dbf4-dependent protein kinase (DDK) complex is a key regulator of DNA replication initiation in eukaryotic cells. This complex is comprised of three core components: Dbf4, a regulatory subunit that binds to and activates the catalytic subunit, DDK; Cdc7, a serine/threonine protein kinase responsible for the catalytic activity of the complex; and Dpb11, a DNA-binding protein that targets the DDK complex to origins of replication. The DDK complex localizes to the nucleus and specifically to replication origins. It is recruited to origins by Dpb11, which binds to specific DNA sequences within the origin recognition complex (ORC). Once assembled at the origin, the DDK complex phosphorylates multiple downstream targets, including the MCM complex, which is a helicase responsible for unwinding DNA during replication. The DDK complex is tightly regulated to ensure that DNA replication occurs only once per cell cycle. The activation of the DDK complex is controlled by the cell cycle checkpoint machinery and the availability of essential cofactors such as Dbf4. In summary, the cellular component of the DDK complex includes:
* **Nucleus:** The complex is localized to the nucleus where DNA replication takes place.
* **Origin of replication:** The DDK complex is specifically targeted to origins of replication, where it plays a crucial role in initiating DNA replication.
* **MCM complex:** The DDK complex phosphorylates the MCM complex, activating its helicase activity for DNA unwinding.
* **Dpb11:** Dpb11 binds to DNA at origins of replication and recruits the DDK complex to its target site.
* **ORC:** The DDK complex interacts with the ORC, a multi-protein complex that binds to origins of replication and initiates the assembly of the pre-replicative complex.
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| Protein | Definition | Taxonomy |
|---|---|---|
| Protein DBF4 homolog A | A protein DBF4 homolog A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UBU7] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| staurosporine | indolocarbazole alkaloid; organic heterooctacyclic compound | apoptosis inducer; bacterial metabolite; EC 2.7.11.13 (protein kinase C) inhibitor; geroprotector | |
| danusertib | piperazines | ||
| pha 767491 | PHA 767491: a Cdc7 inhibitor; structure in first source | pyrrolopyridine | |
| entrectinib | entrectinib : A member of the class of indazoles that is 1H-indazole substituted by [4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzoyl]amino and 3,5-difluorobenzyl groups at positions 3 and 5, respectively. It is a potent inhibitor of TRKA, TRKB, TRKC, ROS1, and ALK (IC50 values of 0.1 to 1.7 nM), and used for the treatment of NTRK, ROS1 and ALK gene fusion-positive solid tumours. entrectinib: inhibits TRK, ROS1, and ALK receptor tyrosine kinases; structure in first source | benzamides; difluorobenzene; indazoles; N-methylpiperazine; oxanes; secondary amino compound; secondary carboxamide | antibacterial agent; antineoplastic agent; apoptosis inducer; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
| nms p937 | NMS P937: a polo-like kinase 1 inhibitor; structure in first source | ||
| nms-p118 | NMS-P118: a PARP-1 inhibitor; structure in first source |