PANTHER family review PTHR10763: IBA propagation assessment for cdc18
Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Gene Ontology annotations Inferred by Curator (IC) using at least one Inferred by Sequence Similarity (ISS) annotation to support the inference
The fission yeast cdc18+ gene product couples S phase to START and mitosis.
p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast.
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cdc18 is required for DNA replication, is transcriptionally activated at START, encodes a nuclear protein peaking at the G1/S transition, and acts at the initiation of DNA replication; its overexpression drives repeated rounds of DNA synthesis without mitosis.
"overexpressing cdc18 is able to bring about repeated rounds of DNA synthesis in the absence of mitosis and of continuing protein synthesis. The level of the cdc18-encoded protein p65cdc18 is periodic in the cell cycle, peaking at the G1 to S phase transition, and p65cdc18 is located in the nucleus when cdc18 is overexpressed."
Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18.
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Chromatin loading of the MCM helicase subunit mcm4 requires ORC (orc1) and cdc18, establishing Cdc18 as essential for pre-RC formation/MCM loading in fission yeast.
"Binding of mcm4 to chromatin requires orc1 and cdc18 (homologous to Cdc6 in budding yeast)."
Expression of Cdc18/Cdc6 and Cdt1 during G2 phase induces initiation of DNA replication.
Requirement of the SCFPop1/Pop2 Ubiquitin Ligase for Degradation of the Fission Yeast S Phase Cyclin Cig2.
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The SCF(Pop1/Pop2) ubiquitin ligase (F-box/WD proteins Pop1 and Pop2) mediates substrate degradation in fission yeast; Cdc18 is an established substrate recognized by this ligase.
"Two F-box/WD proteins Pop1 and Pop2, homologues of budding yeast Cdc4 and human Fbw7, are responsible for Cig2 instability."
The regulation of competence to replicate in meiosis by Cdc6 is conserved during evolution.
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In S. pombe, cdc18 (the Cdc6 homologue) protein synthesis is down-regulated during meiosis, and lack of cdc18 prevents DNA replication in spores, underscoring its requirement for replication competence.
"in S. pombe cdc18 (the S. pombe CDC6 homologue), CDC6 protein synthesis is down regulated during meiosis. As such, the lack of cdc18 prevents DNA replication from occurring in spores"
Cdc18 enforces long-term maintenance of the S phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin.
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Upon replication stalling, Cdc18 persists on chromatin and anchors the Rad3-Rad26 (ATR-ATRIP) checkpoint kinase complex; Rad26 directly binds Cdc18 and is required for Rad3 chromatin recruitment, enabling long-term S-phase checkpoint maintenance.
"Cdc18 plays a pivotal role in checkpoint maintenance by anchoring the Rad3-Rad26 complex to chromatin."
Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin-proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18.
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Pop1 binds Cdc18 in vivo and acts as a recognition factor targeting Cdc18 (and Rum1) for ubiquitin-proteasome degradation, controlling genome ploidy; pop1 mutants accumulate Cdc18.
"Pop1 functions as a recognition factor for Rum1 and Cdc18, which are subsequently ubiquitinated and targeted to the 26S proteasome for degradation."
sud1(+) targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins for degradation and stops unwanted diploidization in fission yeast.
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Sud1/Pop2 binds Cdc18 in a CDK-phosphorylation-dependent manner and is required for its degradation, limiting S phase to one round per cycle and preventing re-replication.
"Sud1-Cdc18 binding requires prior phosphorylation of the Cdc18 polypeptide at CDK consensus sites."
F-box/WD-repeat proteins pop1p and Sud1p/Pop2p form complexes that bind and direct the proteolysis of cdc18p.
Control of DNA rereplication via Cdc2 phosphorylation sites in the origin recognition complex.
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Cdc18 is the limiting replication initiation factor whose deregulation (overexpression and loss of CDK phosphorylation) drives re-replication; Cdc2 phosphorylation of Orp2/Orc2 is partially redundant with regulation of Cdc18 in preventing re-replication.
"Cdc2 phosphorylation of Orp2 may be redundant with regulation of Cdc18 for preventing reinitiation of DNA synthesis."