The gene's position is on chromosome 11q12-q13.[4]
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.[4]
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).[5] 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.
↑Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S (Feb 1996). "Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein". Genomics. 29 (1): 62–9. doi:10.1006/geno.1995.1215. PMID8530102.
↑Seki N, Hayashi A, Hattori A, Kozuma S, Sasaki M, Suzuki Y, Sugano S, Muramatsu M, Saito T (Jan 2000). "cDNA cloning, tissue expression, and chromosomal assignment of a mouse gene, encoding a 127 kDa UV-damaged DNA binding protein which is defective in XPE cells". DNA Res. 6 (5): 319–22. doi:10.1093/dnares/6.5.319. PMID10574459.
Chu G, Chang E (1988). "Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA". Science. 242 (4878): 564–7. doi:10.1126/science.3175673. PMID3175673.
Keeney S, Chang GJ, Linn S (1993). "Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E.". J. Biol. Chem. 268 (28): 21293–300. PMID8407967.
Hwang BJ, Liao JC, Chu G (1996). "Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells". Mutat. Res. 362 (1): 105–17. doi:10.1016/0921-8777(95)00040-2. PMID8538642.
Nichols AF, Ong P, Linn S (1996). "Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype". J. Biol. Chem. 271 (40): 24317–20. doi:10.1074/jbc.271.40.24317. PMID8798680.
Liu W, Nichols AF, Graham JA, et al. (2000). "Nuclear transport of human DDB protein induced by ultraviolet light". J. Biol. Chem. 275 (28): 21429–34. doi:10.1074/jbc.M000961200. PMID10777491.
Chen X, Zhang Y, Douglas L, Zhou P (2002). "UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation". J. Biol. Chem. 276 (51): 48175–82. doi:10.1074/jbc.M106808200. PMID11673459.
Bontron S, Lin-Marq N, Strubin M (2002). "Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2". J. Biol. Chem. 277 (41): 38847–54. doi:10.1074/jbc.M205722200. PMID12151405.
Groisman R, Polanowska J, Kuraoka I, et al. (2003). "The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage". Cell. 113 (3): 357–67. doi:10.1016/S0092-8674(03)00316-7. PMID12732143.
Wertz IE, O'Rourke KM, Zhang Z, et al. (2004). "Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase". Science. 303 (5662): 1371–4. doi:10.1126/science.1093549. PMID14739464.
Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID14743216.