UNIPROT #

Q9H211

PROTEIN NAME

CDT1

SYNONYMS

CDT 1 antibody; cdt1 antibody; CDT1_HUMAN antibody; Chromatin licensing and DNA replication factor 1 antibody; DNA replication factor antibody; DNA replication factor Cdt1 antibody; Double parked antibody; Double parked Drosophila homolog of antibody; Double parked homolog antibody; DUP antibody; Retroviral integration site 1 antibody; Retroviral integration site 2 antibody; Retroviral integration site1 antibody; Retroviral integration site2 antibody; RIS 2 antibody; RIS2 antibody

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.

FUNCTION

Human Cdt1 is a nuclear localizing replication initiation factor that is expressed only during the G1 and S phases of the cell cycle. In conjunction with Cdc18, Cdt1 is required to load the MCM protein Cdc21 onto chromatin at the end of mitosis which is necessary to initiate DNA replication. After S-phase onset, Cdt1 protein levels decrease and are barely detectable in cells in early S-phase or G2. However, Cdt1 mRNA is expressed in S-phase-arrested cells, and its levels do not change dramatically during the cell cycle, suggesting that proteolytic degradation rather than transcriptional controls ensure proper accumulation of Cdt1. Cdt1 can associate with the DNA replication inhibitor geminin, which is present in the S and G2 phases of the cell cycle. Inhibition of DNA replication by geminin in cell-free DNA replication extracts can be reversed by the addition of excess Cdt1. Geminin may be responsible for preventing inappropriate origin firing by targeting Cdt1.