DDB1 explained

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).^[1] 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.

Further reading

• Chu G, Chang E . Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. . Science . 242 . 4878 . 564–7 . 1988 . 3175673 . 10.1126/science.3175673 . 1988Sci...242..564C .
• Lee TH, Elledge SJ, Butel JS . Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. . J. Virol. . 69 . 2 . 1107–14 . 1995 . 7815490 . 10.1128/JVI.69.2.1107-1114.1995. 188683 .
• Keeney S, Eker AP, Brody T . Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein. . Proc. Natl. Acad. Sci. U.S.A. . 91 . 9 . 4053–6 . 1994 . 8171034 . 10.1073/pnas.91.9.4053 . 43721 . 1994PNAS...91.4053K . etal. free .
• Keeney S, Chang GJ, Linn S . Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. . J. Biol. Chem. . 268 . 28 . 21293–300 . 1993 . 10.1016/S0021-9258(19)36923-6 . 8407967 . free .
• Hwang BJ, Liao JC, Chu G . Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells. . Mutat. Res. . 362 . 1 . 105–17 . 1996 . 8538642 . 10.1016/0921-8777(95)00040-2.
• Nichols AF, Ong P, Linn S . Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. . J. Biol. Chem. . 271 . 40 . 24317–20 . 1996 . 8798680 . 10.1074/jbc.271.40.24317 . free .
• Liu W, Nichols AF, Graham JA . Nuclear transport of human DDB protein induced by ultraviolet light. . J. Biol. Chem. . 275 . 28 . 21429–34 . 2000 . 10777491 . 10.1074/jbc.M000961200 . etal. free .
• Martinez E, Palhan VB, Tjernberg A . Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. . Mol. Cell. Biol. . 21 . 20 . 6782–95 . 2001 . 11564863 . 10.1128/MCB.21.20.6782-6795.2001 . 99856 . etal.
• Chen X, Zhang Y, Douglas L, Zhou P . UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. . J. Biol. Chem. . 276 . 51 . 48175–82 . 2002 . 11673459 . 10.1074/jbc.M106808200 . free .
• Rapić-Otrin V, McLenigan MP, Bisi DC . Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. . Nucleic Acids Res. . 30 . 11 . 2588–98 . 2002 . 12034848 . 10.1093/nar/30.11.2588 . 117178 . etal.
• Bergametti F, Sitterlin D, Transy C . Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex. . J. Virol. . 76 . 13 . 6495–501 . 2002 . 12050362 . 10.1128/JVI.76.13.6495-6501.2002 . 136256 .
• Bontron S, Lin-Marq N, Strubin M . 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 . 2002 . 12151405 . 10.1074/jbc.M205722200 . free .
• Andrejeva J, Poole E, Young DF . The p127 subunit (DDB1) of the UV-DNA damage repair binding protein is essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. . J. Virol. . 76 . 22 . 11379–86 . 2002 . 12388698 . 10.1128/JVI.76.22.11379-11386.2002 . 136798 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Groisman R, Polanowska J, Kuraoka I . 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 . 2003 . 12732143 . 10.1016/S0092-8674(03)00316-7 . 11639677 . etal. free .
• Leupin O, Bontron S, Strubin M . Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities. . J. Virol. . 77 . 11 . 6274–83 . 2003 . 12743284 . 10.1128/JVI.77.11.6274-6283.2003 . 154990 .
• Wertz IE, O'Rourke KM, Zhang Z . Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. . Science . 303 . 5662 . 1371–4 . 2004 . 14739464 . 10.1126/science.1093549 . 2004Sci...303.1371W . 40501515 . etal.
• Bouwmeester T, Bauch A, Ruffner H . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. . Nat. Cell Biol. . 6 . 2 . 97–105 . 2004 . 14743216 . 10.1038/ncb1086 . 11683986 . etal.

Notes and References

1. 10.1016/j.molcel.2007.06.001 . 17588513 . 26 . 6 . DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase . 2007 . Molecular Cell . 775–780 . Lee J. free .