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DDB1

{{Short description|Protein-coding gene in the species Homo sapiens}}

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{{Infobox gene}}

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).{{cite journal| doi=10.1016/j.molcel.2007.06.001 | pmid=17588513 | volume=26 | issue=6 | title=DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase | year=2007 | journal=Molecular Cell | pages=775–780 | vauthors=Lee J| doi-access=free }} 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.

References

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{{cite journal |vauthors=Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S |title=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 |journal=Genomics |volume=29 |issue=1 |pages=62–9 |date=Feb 1996 |pmid=8530102 |doi=10.1006/geno.1995.1215 }}

{{cite journal |vauthors=Seki N, Hayashi A, Hattori A, Kozuma S, Sasaki M, Suzuki Y, Sugano S, Muramatsu M, Saito T |title=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 |journal=DNA Res |volume=6 |issue=5 |pages=319–22 |date=Jan 2000 |pmid=10574459 |doi =10.1093/dnares/6.5.319 |doi-access=free }}

{{cite web |title=Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1642}}

{{cite journal |last1=Iovine |first1=Barbara |last2=Iannella |first2=Maria Luigia |last3=Bevilacqua |first3=Maria Assunta |title=Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions |journal=The International Journal of Biochemistry & Cell Biology |volume=43 |issue=12 |pages=1664–1667 |publisher=Elsevier |date=2011 |url=https://www.researchgate.net/publication/51681484 |doi=10.1016/j.biocel.2011.09.001|pmid=21959250 }}

{{cite journal |vauthors=Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG |title=Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo |journal=Mol. Cell. Biol. |volume=21 |issue=20 |pages=6782–95 |date=October 2001 |pmid=11564863 |pmc=99856 |doi=10.1128/MCB.21.20.6782-6795.2001 }}

{{cite journal |vauthors=Huang J, Chen J |title=VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation |journal=Oncogene |volume=27 |issue=29 |pages=4056–64 |date=July 2008 |pmid=18332868 |doi=10.1038/onc.2008.44 |s2cid=23628888 |doi-access= }}

{{cite journal |vauthors=Bergametti F, Sitterlin D, Transy C |title=Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex |journal=J. Virol. |volume=76 |issue=13 |pages=6495–501 |date=July 2002 |pmid=12050362 |pmc=136256 |doi=10.1128/JVI.76.13.6495-6501.2002}}

{{cite journal |vauthors=Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapić-Otrin V |title=The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A |journal=Cancer Res. |volume=68 |issue=13 |pages=5014–22 |date=July 2008 |pmid=18593899 |doi=10.1158/0008-5472.CAN-07-6162 |doi-access=free }}

{{cite journal |vauthors=Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A |title=PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex |journal=Genes Dev. |volume=22 |issue=18 |pages=2496–506 |date=September 2008 |pmid=18794347 |pmc=2546691 |doi=10.1101/gad.1676108 }}

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Further reading

{{refbegin | 2}}

  • {{cite journal | vauthors=Chu G, Chang E |title=Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. |journal=Science |volume=242 |issue= 4878 |pages= 564–7 |year= 1988 |pmid= 3175673 |doi=10.1126/science.3175673 |bibcode=1988Sci...242..564C }}
  • {{cite journal | vauthors=Lee TH, Elledge SJ, Butel JS |title=Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. |journal=J. Virol. |volume=69 |issue= 2 |pages= 1107–14 |year= 1995 |pmid= 7815490 |doi= 10.1128/JVI.69.2.1107-1114.1995| pmc=188683 }}
  • {{cite journal | vauthors=Keeney S, Eker AP, Brody T |title=Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 9 |pages= 4053–6 |year= 1994 |pmid= 8171034 |doi=10.1073/pnas.91.9.4053 | pmc=43721 |bibcode=1994PNAS...91.4053K |display-authors=etal|url=https://repub.eur.nl/pub/3066/9600.pdf|doi-access=free }}
  • {{cite journal | vauthors=Keeney S, Chang GJ, Linn S |title=Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. |journal=J. Biol. Chem. |volume=268 |issue= 28 |pages= 21293–300 |year= 1993 |doi=10.1016/S0021-9258(19)36923-6 |pmid= 8407967 |doi-access=free }}
  • {{cite journal | vauthors=Hwang BJ, Liao JC, Chu G |title=Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells. |journal=Mutat. Res. |volume=362 |issue= 1 |pages= 105–17 |year= 1996 |pmid= 8538642 |doi= 10.1016/0921-8777(95)00040-2|doi-access=free }}
  • {{cite journal | vauthors=Nichols AF, Ong P, Linn S |title=Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. |journal=J. Biol. Chem. |volume=271 |issue= 40 |pages= 24317–20 |year= 1996 |pmid= 8798680 |doi=10.1074/jbc.271.40.24317 |doi-access=free }}
  • {{cite journal | vauthors=Liu W, Nichols AF, Graham JA |title=Nuclear transport of human DDB protein induced by ultraviolet light. |journal=J. Biol. Chem. |volume=275 |issue= 28 |pages= 21429–34 |year= 2000 |pmid= 10777491 |doi= 10.1074/jbc.M000961200 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Martinez E, Palhan VB, Tjernberg A |title=Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. |journal=Mol. Cell. Biol. |volume=21 |issue= 20 |pages= 6782–95 |year= 2001 |pmid= 11564863 |doi= 10.1128/MCB.21.20.6782-6795.2001 | pmc=99856 |display-authors=etal}}
  • {{cite journal | vauthors=Chen X, Zhang Y, Douglas L, Zhou P |title=UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. |journal=J. Biol. Chem. |volume=276 |issue= 51 |pages= 48175–82 |year= 2002 |pmid= 11673459 |doi= 10.1074/jbc.M106808200 |doi-access= free }}
  • {{cite journal | vauthors=Rapić-Otrin V, McLenigan MP, Bisi DC |title=Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. |journal=Nucleic Acids Res. |volume=30 |issue= 11 |pages= 2588–98 |year= 2002 |pmid= 12034848 |doi=10.1093/nar/30.11.2588 | pmc=117178 |display-authors=etal}}
  • {{cite journal | vauthors=Bergametti F, Sitterlin D, Transy C |title=Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex. |journal=J. Virol. |volume=76 |issue= 13 |pages= 6495–501 |year= 2002 |pmid= 12050362 |doi=10.1128/JVI.76.13.6495-6501.2002 | pmc=136256 }}
  • {{cite journal | vauthors=Bontron S, Lin-Marq N, Strubin M |title=Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2. |journal=J. Biol. Chem. |volume=277 |issue= 41 |pages= 38847–54 |year= 2002 |pmid= 12151405 |doi= 10.1074/jbc.M205722200 |doi-access= free }}
  • {{cite journal | vauthors=Andrejeva J, Poole E, Young DF |title=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. |journal=J. Virol. |volume=76 |issue= 22 |pages= 11379–86 |year= 2002 |pmid= 12388698 |doi=10.1128/JVI.76.22.11379-11386.2002 | pmc=136798 |display-authors=etal}}
  • {{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Groisman R, Polanowska J, Kuraoka I |title=The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. |journal=Cell |volume=113 |issue= 3 |pages= 357–67 |year= 2003 |pmid= 12732143 |doi=10.1016/S0092-8674(03)00316-7 |s2cid=11639677 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Leupin O, Bontron S, Strubin M |title=Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities. |journal=J. Virol. |volume=77 |issue= 11 |pages= 6274–83 |year= 2003 |pmid= 12743284 |doi=10.1128/JVI.77.11.6274-6283.2003 | pmc=154990 }}
  • {{cite journal | vauthors=Wertz IE, O'Rourke KM, Zhang Z |title=Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. |journal=Science |volume=303 |issue= 5662 |pages= 1371–4 |year= 2004 |pmid= 14739464 |doi= 10.1126/science.1093549 |bibcode=2004Sci...303.1371W |s2cid=40501515 |display-authors=etal|url=https://authors.library.caltech.edu/52147/7/Wertz.SOM.pdf }}
  • {{cite journal | vauthors=Bouwmeester T, Bauch A, Ruffner H |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97–105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 |s2cid=11683986 |display-authors=etal}}

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{{PDB Gallery|geneid=1642}}

{{DNA repair}}