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DDB1
Introduction
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.[1][2][3]
Protein
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
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.
Interactions
Interactions
DDB1 has been shown to interact with Transcription initiation protein SPT3 homolog,[6] GCN5L2,[7] DDB2,[8][9] CUL4A,[9] CUL4B[9] and P21.[10]
References
References
- β 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): 62β9. doi:10.1006/geno.1995.1215. PMIDΒ 8530102.
- β 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): 319β22. doi:10.1093/dnares/6.5.319. PMIDΒ 10574459.
- β “Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa”.
- β 4.0 4.1 Iovine, Barbara; Iannella, Maria Luigia; Bevilacqua, Maria Assunta (2011). “Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions” (PDF). The International Journal of Biochemistry & Cell Biology. Elsevier. 43: 1664β1667. doi:10.1016/j.biocel.2011.09.001.
- β Lee J (2007). “DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase”. Molecular Cell. 26: 775β780. doi:10.1016/j.molcel.2007.06.001.
- β Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG (October 2001). “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): 6782β95. doi:10.1128/MCB.21.20.6782-6795.2001. PMCΒ 99856. PMIDΒ 11564863.
- β Huang J, Chen J (July 2008). “VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation”. Oncogene. 27 (29): 4056β64. doi:10.1038/onc.2008.44. PMIDΒ 18332868.
- β Bergametti F, Sitterlin D, Transy C (July 2002). “Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex”. J. Virol. 76 (13): 6495β501. doi:10.1128/JVI.76.13.6495-6501.2002. PMCΒ 136256. PMIDΒ 12050362.
- β 9.0 9.1 9.2 Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, RapiΔ-Otrin V (July 2008). “The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A”. Cancer Res. 68 (13): 5014β22. doi:10.1158/0008-5472.CAN-07-6162. PMIDΒ 18593899.
- β Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (September 2008). “PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex”. Genes Dev. 22 (18): 2496β506. doi:10.1101/gad.1676108. PMCΒ 2546691. PMIDΒ 18794347.
Further reading
Further reading
- Chu G, Chang E (1988). “Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA”. Science. 242 (4878): 564β7. doi:10.1126/science.3175673. PMIDΒ 3175673.
- Lee TH, Elledge SJ, Butel JS (1995). “Hepatitis B virus X protein interacts with a probable cellular DNA repair protein”. J. Virol. 69 (2): 1107β14. PMCΒ 188683. PMIDΒ 7815490.
- Keeney S, Eker AP, Brody T, et al. (1994). “Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein” (PDF). Proc. Natl. Acad. Sci. U.S.A. 91 (9): 4053β6. doi:10.1073/pnas.91.9.4053. PMCΒ 43721. PMIDΒ 8171034.
- 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): 21293β300. PMIDΒ 8407967.
- 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): 105β17. doi:10.1016/0921-8777(95)00040-2. PMIDΒ 8538642.
- Nichols AF, Ong P, Linn S (1996). “Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype”. J. Biol. Chem. 271 (40): 24317β20. doi:10.1074/jbc.271.40.24317. PMIDΒ 8798680.
- Liu W, Nichols AF, Graham JA, et al. (2000). “Nuclear transport of human DDB protein induced by ultraviolet light”. J. Biol. Chem. 275 (28): 21429β34. doi:10.1074/jbc.M000961200. PMIDΒ 10777491.
- Martinez E, Palhan VB, Tjernberg A, et al. (2001). “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): 6782β95. doi:10.1128/MCB.21.20.6782-6795.2001. PMCΒ 99856. PMIDΒ 11564863.
- 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): 48175β82. doi:10.1074/jbc.M106808200. PMIDΒ 11673459.
- RapiΔ-Otrin V, McLenigan MP, Bisi DC, et al. (2002). “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): 2588β98. doi:10.1093/nar/30.11.2588. PMCΒ 117178. PMIDΒ 12034848.
- Bergametti F, Sitterlin D, Transy C (2002). “Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex”. J. Virol. 76 (13): 6495β501. doi:10.1128/JVI.76.13.6495-6501.2002. PMCΒ 136256. PMIDΒ 12050362.
- 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): 38847β54. doi:10.1074/jbc.M205722200. PMIDΒ 12151405.
- Andrejeva J, Poole E, Young DF, et al. (2002). “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): 11379β86. doi:10.1128/JVI.76.22.11379-11386.2002. PMCΒ 136798. PMIDΒ 12388698.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). “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): 16899β903. doi:10.1073/pnas.242603899. PMCΒ 139241. PMIDΒ 12477932.
- 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): 357β67. doi:10.1016/S0092-8674(03)00316-7. PMIDΒ 12732143.
- Leupin O, Bontron S, Strubin M (2003). “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): 6274β83. doi:10.1128/JVI.77.11.6274-6283.2003. PMCΒ 154990. PMIDΒ 12743284.
- 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): 1371β4. doi:10.1126/science.1093549. PMIDΒ 14739464.
- 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): 97β105. doi:10.1038/ncb1086. PMIDΒ 14743216.