DTL
Description
The DTL (denticleless E3 ubiquitin protein ligase homolog) is a protein-coding gene located on chromosome 1.
DTL, a protein crucial for cell cycle control, DNA damage response, and translesion DNA synthesis, is an important part of a complex called DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase. This complex, also known as CRL4(CDT2), is essential for tagging and breaking down proteins. DTL plays a critical role as a substrate-specific adapter for this complex, ensuring the proper degradation of specific proteins involved in various cellular processes. For instance, DTL is involved in the degradation of CDT1, which is important for DNA replication, and CDKN1A/p21(CIP1), which controls replication licensing. Furthermore, DTL interacts with other proteins, like CRY1, contributing to the regulation of the circadian clock.
DTL is a protein that acts as a substrate-specific adapter for a protein complex called DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase. This complex is essential for regulating the cell cycle, responding to DNA damage, and facilitating translesion DNA synthesis. The DCX(DTL) complex, also known as CRL4(CDT2), mediates the tagging and breakdown of several proteins including CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A, and SDE2. The breakdown of CDT1 in response to DNA damage is crucial for maintaining proper cell cycle control during DNA replication. Degradation of CDKN1A/p21(CIP1) during the S phase or after exposure to UV radiation is vital for regulating replication licensing. The degradation of KMT5A is important for properly regulating mechanisms like TGF-beta signaling, cell cycle progression, DNA repair, and cell migration. Most proteins that undergo degradation by this complex require interaction with PCNA, a protein involved in DNA replication. These substrates bind to PCNA through their PIP-box, and those with a specific 'K+4' motif in this box recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the monoubiquitination of PCNA at 'Lys-164', playing a role in PCNA-dependent translesion DNA synthesis. The DDB1-CUL4A-DTL E3 ligase complex also regulates the circadian clock by mediating the ubiquitination and breakdown of CRY1.
DTL is also known as CDT2, DCAF2, L2DTL, RAMP.
