UNIPROT #

Q9H211

PROTEIN NAME

DNA replication factor Cdt1

GENE NAME

CDT1

SYNONYMS

DUP, CDT1

SEQUENCE SIMILARITIES

Belongs to the Cdt1 family.

DEVELOPMENTAL STAGE

Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases.

POST-TRANSLATIONAL MODIFICATION

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. The interaction with GMNN protects it against ubiquitination. Deubiquitinated by USP37.; Phosphorylation by cyclin A-dependent kinases at Thr-29 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. Phosphorylated at Thr-29 by MAPK8/JNK1, which blocks replication licensing in response to stress. Binding to GMNN is not affected by phosphorylation.

SUBCELLULAR LOCATION

Nucleus. Chromosome, centromere, kinetochore. Note=Transiently localizes to kinetochores during prometaphase and metaphase.

FUNCTION

Required for both DNA replication and mitosis. 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. Potential oncogene (By similarity).