DDB2
Description
The DDB2 (damage specific DNA binding protein 2) is a protein-coding gene located on chromosome 11.
DNA damage-binding protein 2 is a protein that in humans is encoded by the DDB2 gene.
== Structure == As indicated by Rapić-Otrin et al. in 2003, the DDB2 gene is located on human chromosome 11p11.2, spans a region of approximately 24 – 26 kb and includes 10 exons. The DDB2 protein contains five putative WD40 repeats (sequences of about 40 amino acids that can interact with each other) positioned downstream from the second exon. The WD40 motif identified in DDB2 is characteristic of proteins involved in the recognition of chromatin proteins. The C-terminal region of DDB2 (a 48 kDa molecular weight protein) is essential for binding to DDB1 (a larger 127 kDa protein). Together, the two proteins form a UV-damaged DNA binding protein complex (UV-DDB).
== Deficiency in humans == If humans have a mutation in each copy of their DDB2 gene, this causes a mild form of the human disease xeroderma pigmentosum, called XPE. Patients in the XPE group have mild dermatological manifestations and are neurologically unaffected. Mutation in the DDB2 gene causes a deficiency in nucleotide excision repair of DNA. This deficiency is also mild, showing 40 to 60% of normal repair capability and a modest sensitivity to UV light in comparison to the sensitivities of cells defective in the other XP genes XPA, XPB, XPC, XPD, XPF and XPG.
== Function ==
=== Binding to damaged DNA === As shown by Wittschieben et al., when DDB2 is in a complex with DDB1, forming the heterodimer DDB, this complex binds strongly to DNA containing one type of UV light-induced photoproduct [the (6-4) photoproduct], to DNA with an abasic site, to DNA containing mismatches without a covalent lesion, and to “compound” lesions containing both mismatches and lesions. The heterodimer DDB binds with intermediate strength to DNA containing another UV light-induced photoproduct (the cyclobutane pyrimidine dimer), and binds weakly to DNA that has no DNA damage.
DDB2 is a protein involved in both DNA repair and protein ubiquitination. It is a core component of the UV-DDB complex, which recognizes UV-induced DNA damage and recruits proteins of the nucleotide excision repair pathway (NER) to initiate repair. The UV-DDB complex binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites, and short mismatches. DDB2 also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1. This complex ubiquitinates histone H2A, histone H3, and histone H4 at sites of UV-induced DNA damage, facilitating their removal from the nucleosome and promoting subsequent DNA repair. The DDB2-CUL4-ROC1 complex also ubiquitinates XPC, enhancing its DNA-binding and promoting NER. Additionally, it ubiquitinates KAT7/HBO1 in response to DNA damage, leading to its degradation.
DDB2 is also known as DDBB, UV-DDB2, XPE.
