Eukaryotic DNA replication starts in two steps that are separated in the cell cycle. In G1, the origin recognition complex (ORC) binds replication origins and, with Cdc6 and Cdt1 (Double parked in Drosophila), loads the MCM2-7 helicase core as an inactive double hexamer around double-stranded DNA; this is origin licensing. In S phase, the Dbf4-dependent kinase (Cdc7 with its regulatory subunit Chiffon) and cyclin-dependent kinases trigger the recruitment of Cdc45 and the four-subunit GINS complex onto MCM2-7, forming the active CMG (Cdc45-MCM-GINS) helicase that unwinds DNA at the replication fork. Restricting licensing to G1 and activation to S phase ensures that each origin fires only once per cell cycle.
Boundary. The module covers origin recognition, MCM2-7 loading and helicase activation. The FlyBase groups CMG, GINS and MCM2-7 overlap; MCM2-7 subunits appear both in the loaded MCM2-7 part and in the CMG part, and GINS is represented inside the CMG part rather than as a separate part. Cdc6 and dup (Cdt1) are not FlyBase members of these groups and were added as textbook licensing factors. Other firing factors (for example Mcm10, Treslin/Sld3 and TopBP1/Dpb11 homologs) and the replicative polymerases (see dmel_dna_polymerase_complexes) are outside the module. FlyBase groups realized by this module: ORC (FBgg0000510), CMG (FBgg0001612), GINS (FBgg0001613), MCM2-7 (FBgg0001614), DDK (FBgg0002115). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_replication_origin_licensing_activation.yaml. None of the member genes has a gene review in this repository yet.
All recommended fields populated.
✗ none found
No MODULE:dmel_replication_origin_licensing_activation deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.
0 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (2 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| ddk_complex/cdc7 | Cdc7 UniProtKB:Q9W3Y1 Complex Unit |
protein serine/threonine kinase activity GO:0004674 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| cmg_complex | PROTEIN_COMPLEX Gene |
DNA helicase activity GO:0003678 |
Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews. |
0 complete review(s) · 0 with deep research · 21 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| dup A0A0B4LGJ6 | ✗ | — | — |
| Orc3 A1Z996 | ✗ | — | — |
| Orc1 O16810 | ✗ | — | — |
| Cdc45 O96989 | ✗ | — | — |
| Mcm2 P49735 | ✗ | — | — |
| Orc2 Q24168 | ✗ | — | — |
| Orc5 Q24169 | ✗ | — | — |
| dpa Q26454 | ✗ | — | — |
| chif Q9NK54 | ✗ | — | — |
| Mcm6 Q9V461 | ✗ | — | — |
| Sld5 Q9VBI1 | ✗ | — | — |
| Mcm5 Q9VGW6 | ✗ | — | — |
| Psf2 Q9VQY9 | ✗ | — | — |
| Cdc6 Q9VSM9 | ✗ | — | — |
| Psf1 Q9W0I7 | ✗ | — | — |
| Orc4 Q9W102 | ✗ | — | — |
| Psf3 Q9W2V7 | ✗ | — | — |
| Cdc7 Q9W3Y1 | ✗ | — | — |
| Mcm7 Q9XYU0 | ✗ | — | — |
| Mcm3 Q9XYU1 | ✗ | — | — |
| Orc6 Q9Y1B2 | ✗ | — | — |
ORC-dependent loading of the MCM2-7 helicase onto origins and its DDK-triggered conversion into the active CMG helicase.
Six-subunit complex that binds replication origins and recruits the licensing machinery.
Cdc6 and Cdt1 (Double parked) cooperate with ORC to load MCM2-7 onto origin DNA. They are not members of the FlyBase groups and are added as textbook licensing factors.
Heterohexameric AAA+ helicase motor (Mcm2, Mcm3, Mcm4/Dpa, Mcm5, Mcm6, Mcm7) loaded as an inactive double hexamer at licensed origins.
Cdc7 kinase with its Dbf4-family regulatory subunit Chiffon; DDK phosphorylates loaded MCM2-7 to promote CMG assembly.
Active helicase formed when Cdc45 and GINS (Psf1, Psf2, Psf3, Sld5) join MCM2-7. GINS is a stable four-subunit subcomplex of CMG.