DDB1
Description
The DDB1 (damage specific DNA binding protein 1) is a protein-coding gene located on chromosome 11.
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.
== Gene == The gene's position is on chromosome 11q12-q13.
== Protein == The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed of a large and a small (DDB2) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa.
== Function == As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as nucleotide excision repair. Since then, researchers have found that DDB1 primarily functions as a core component of the CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs). These DCAFs are often ubiquitin ligase substrates and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling (Cdt2) and more.
== Interactions == DDB1 has been shown to interact with Transcription initiation protein SPT3 homolog, GCN5L2, DDB2, CUL4A, CUL4B and P21.
DDB1 is a protein involved in both DNA repair and protein ubiquitination. It functions as a core component of two distinct complexes: the UV-DDB complex and the DCX (DDB1-CUL4-X-box) complexes. The UV-DDB complex recognizes UV-induced DNA damage, such as cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites, and short mismatches, and recruits proteins of the nucleotide excision repair (NER) pathway to initiate DNA repair. The DCX complex functions as an E3 ubiquitin-protein ligase, mediating the ubiquitination and subsequent proteasomal degradation of target proteins. The specificity of the DCX complex is determined by the variable substrate recognition component recruited by DDB1. Different DCX complexes, such as DCX(DDB2), DCX(DTL), and DCX(ERCC8), play roles in various cellular processes, including histone ubiquitination, XPC ubiquitination, CDT1 polyubiquitination, TP53 ubiquitination, and transcription-coupled repair (TCR). The DDB1-CUL4A-DTL E3 ligase complex also regulates the circadian clock function by mediating CRY1 ubiquitination and degradation. DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver. Additionally, DDB1 is essential for oocyte maintenance at the primordial follicle stage and for proper zygotic genome activation and genome reprogramming.
DDB1 is also known as DDBA, UV-DDB1, WHIKERS, XAP1, XPCE, XPE, XPE-BF.
