CDT1

The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]

Chromatin Licensing And DNA Replication Factor 1

Required for both DNA replication and mitosis (PubMed:11125146, PubMed:22581055, PubMed:21856198, PubMed:14993212, PubMed:26842564).
DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC)(PubMed:14672932).
Required also for mitosis by promoting stable kinetochore-microtubule attachments (PubMed:22581055).
Potential oncogene (By similarity).

Attachment of mitotic spindle microtubules to kinetochore Source: UniProtKB
Cell division Source: CAFA
Chromosome segregation Source: UniProtKB
Deactivation of mitotic spindle assembly checkpoint Source: CAFA
DNA replication checkpoint Source: UniProtKB
DNA replication initiation Source: Reactome
DNA replication preinitiation complex assembly Source: CAFA
Kinetochore organization Source: CAFA
Mitotic cell cycle Source: UniProtKB
Negative regulation of protein localization to kinetochore Source: CAFA
Positive regulation of chromatin binding Source: CAFA
Positive regulation of DNA-dependent DNA replication Source: CAFA
Positive regulation of DNA replication Source: UniProtKB
Positive regulation of protein-containing complex assembly Source: CAFA
Positive regulation of protein localization to kinetochore Source: CAFA
Pre-replicative complex assembly Source: Reactome
Regulation of chromosome organization Source: CAFA
Regulation of DNA-dependent DNA replication initiation Source: UniProtKB
Regulation of DNA replication origin binding Source: CAFA
Regulation of nuclear cell cycle DNA replication Source: Ensembl
Regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Reactome
Response to sorbitol Source: CAFA

Nucleus; Kinetochore. Transiently localizes to kinetochores during prometaphase and metaphase.

Meier-Gorlin syndrome 4 (MGORS4): A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.

Two independent E3 ubiquitin ligase complexes, SCF(SKP2) and the DCX(DTL) complex, mediated CDT1 degradation in S phase. Ubiquitinated by the DCX(DTL) complex, in response to DNA damage, leading to its degradation. Ubiquitination by the DCX(DTL) complex is necessary to ensure proper cell cycle regulation and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Phosphorylation at Thr-29 by CDK2 targets CDT1 for ubiquitination by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation (PubMed:14993212). The interaction with GMNN protects it against ubiquitination. Deubiquitinated by USP37 (PubMed:27296872).
Phosphorylation by cyclin A-dependent kinases at Thr-29 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation (PubMed:14993212). Phosphorylated at Thr-29 by MAPK8/JNK1, which blocks replication licensing in response to stress (PubMed:21856198). Binding to GMNN is not affected by phosphorylation.