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Gene Review

DDB2  -  damage-specific DNA binding protein 2, 48kDa

Homo sapiens

Synonyms: DDB p48 subunit, DDBB, DDBb, DNA damage-binding protein 2, Damage-specific DNA-binding protein 2, ...
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Disease relevance of DDB2


High impact information on DDB2

  • Here, we show that DDB2 and CSA are each integrated into nearly identical complexes via interaction with DDB1 [6].
  • These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER [6].
  • The mice exhibited significantly enhanced skin carcinogenesis in response to UV-irradiation, and cells from the DDB2(-/-) mice were abnormally resistant to killing by the radiation and had diminished UV-induced, p53-mediated apoptosis [7].
  • Mutations in the human DDB2 gene give rise to xeroderma pigmentosum group E, a disease characterized by increased skin tumorigenesis in response to UV-irradiation [7].
  • DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen [7].

Chemical compound and disease context of DDB2


Biological context of DDB2

  • To better define the role of DDB2 in the cellular response to DNA damage, we purified all four forms of DDB2 and analyzed their DNA binding properties and their effects on mammalian nucleotide excision repair [9].
  • Besides confirming that the true XP-E phenotype is DDB(-), resulting from defects in a single gene, DDB2, our results identify the functional domains of the corresponding p48 protein [10].
  • Hence, HBx-mediated cell death can be relieved by increased levels of DDB2, an effect that is not observed with a naturally occurring mutant of DDB2 that lacks DDB1-binding activity [4].
  • BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation [11].
  • Antisense abrogation of BRCA1 expression abrogates upregulation of DDB2 after UVC or cisplatin exposure [11].

Anatomical context of DDB2

  • Transient expression analysis in HeLa cells using a luciferase reporter system indicated the presence of core promoters located within 292 bp (DDB1) and 220 bp (DDB2) upstream of the putative transcription initiation sites [2].
  • The cisplatin-resistant cell line (HR3) exhibits enhanced expression of DDB2 and cross-resistance to UV-induced activation of apoptosis and caspases [12].
  • E6 fibroblasts exhibited markedly reduced basal and induced levels of mRNA encoding DDB2, another protein implicated in early events in global NER [13].
  • In contrast, E6 or E6/E7 keratinocytes possessed basal DDB2 mRNA levels that were not significantly altered relative to control cells, although little induction occurred following UV radiation [13].
  • We show that the nuclear levels of DDB1 and DDB2 are tightly regulated in hepatocytes [14].

Associations of DDB2 with chemical compounds


Physical interactions of DDB2

  • Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties [9].

Regulatory relationships of DDB2


Other interactions of DDB2


Analytical, diagnostic and therapeutic context of DDB2


  1. Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53. Itoh, T., O'Shea, C., Linn, S. Mol. Cell. Biol. (2003) [Pubmed]
  2. Basal transcriptional regulation of human damage-specific DNA-binding protein genes DDB1 and DDB2 by Sp1, E2F, N-myc and NF1 elements. Nichols, A.F., Itoh, T., Zolezzi, F., Hutsell, S., Linn, S. Nucleic Acids Res. (2003) [Pubmed]
  3. Xeroderma pigmentosum complementation group E and UV-damaged DNA-binding protein. Tang, J., Chu, G. DNA Repair (Amst.) (2002) [Pubmed]
  4. Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2. Bontron, S., Lin-Marq, N., Strubin, M. J. Biol. Chem. (2002) [Pubmed]
  5. Restoration of UV sensitivity in UV-resistant HeLa cells by antisense-mediated depletion of damaged DNA-binding protein 2 (DDB2). Sun, N.K., Kamarajan, P., Huang, H., Chao, C.C. FEBS Lett. (2002) [Pubmed]
  6. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Groisman, R., Polanowska, J., Kuraoka, I., Sawada, J., Saijo, M., Drapkin, R., Kisselev, A.F., Tanaka, K., Nakatani, Y. Cell (2003) [Pubmed]
  7. DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen. Itoh, T., Cado, D., Kamide, R., Linn, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice. Tan, T., Chu, G. Mol. Cell. Biol. (2002) [Pubmed]
  9. Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties. Kulaksiz, G., Reardon, J.T., Sancar, A. Mol. Cell. Biol. (2005) [Pubmed]
  10. True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product. Rapić-Otrin, V., Navazza, V., Nardo, T., Botta, E., McLenigan, M., Bisi, D.C., Levine, A.S., Stefanini, M. Hum. Mol. Genet. (2003) [Pubmed]
  11. BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation. Takimoto, R., MacLachlan, T.K., Dicker, D.T., Niitsu, Y., Mori, T., el-Deiry, W.S. Cancer Biol. Ther. (2002) [Pubmed]
  12. Cross-resistance to death ligand-induced apoptosis in cisplatin-selected HeLa cells associated with overexpression of DDB2 and subsequent induction of cFLIP. Sun, C.L., Chao, C.C. Mol. Pharmacol. (2005) [Pubmed]
  13. Proficient global nucleotide excision repair in human keratinocytes but not in fibroblasts deficient in p53. Ferguson, B.E., Oh, D.H. Cancer Res. (2005) [Pubmed]
  14. DDB2 induces nuclear accumulation of the hepatitis B virus X protein independently of binding to DDB1. Nag, A., Datta, A., Yoo, K., Bhattacharyya, D., Chakrabortty, A., Wang, X., Slagle, B.L., Costa, R.H., Raychaudhuri, P. J. Virol. (2001) [Pubmed]
  15. In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product. Fitch, M.E., Nakajima, S., Yasui, A., Ford, J.M. J. Biol. Chem. (2003) [Pubmed]
  16. Characterization of T-DNA insertion mutants and RNAi silenced plants of Arabidopsis thaliana UV-damaged DNA binding protein 2 (AtUV-DDB2). Koga, A., Ishibashi, T., Kimura, S., Uchiyama, Y., Sakaguchi, K. Plant Mol. Biol. (2006) [Pubmed]
  17. Interaction between UV-damaged DNA binding activity proteins and the c-Abl tyrosine kinase. Cong, F., Tang, J., Hwang, B.J., Vuong, B.Q., Chu, G., Goff, S.P. J. Biol. Chem. (2002) [Pubmed]
  18. The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts. Fitch, M.E., Cross, I.V., Turner, S.J., Adimoolam, S., Lin, C.X., Williams, K.G., Ford, J.M. DNA Repair (Amst.) (2003) [Pubmed]
  19. The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells. Nag, A., Bondar, T., Shiv, S., Raychaudhuri, P. Mol. Cell. Biol. (2001) [Pubmed]
  20. The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Kapetanaki, M.G., Guerrero-Santoro, J., Bisi, D.C., Hsieh, C.L., Rapić-Otrin, V., Levine, A.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  21. Tumor suppressor p53 dependent recruitment of nucleotide excision repair factors XPC and TFIIH to DNA damage. Wang, Q.E., Zhu, Q., Wani, M.A., Wani, G., Chen, J., Wani, A.A. DNA Repair (Amst.) (2003) [Pubmed]
  22. UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2. Wang, Q.E., Zhu, Q., Wani, G., Chen, J., Wani, A.A. Carcinogenesis (2004) [Pubmed]
  23. 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. Dualan, R., Brody, T., Keeney, S., Nichols, A.F., Admon, A., Linn, S. Genomics (1995) [Pubmed]
  24. Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case-control study. Hu, Z., Shao, M., Yuan, J., Xu, L., Wang, F., Wang, Y., Yuan, W., Qian, J., Ma, H., Wang, Y., Liu, H., Chen, W., Yang, L., Jin, G., Huo, X., Chen, F., Jin, L., Wei, Q., Huang, W., Lu, D., Wu, T., Shen, H. Carcinogenesis (2006) [Pubmed]
  25. DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex. Matsuda, N., Azuma, K., Saijo, M., Iemura, S., Hioki, Y., Natsume, T., Chiba, T., Tanaka, K., Tanaka, K. DNA Repair (Amst.) (2005) [Pubmed]
  26. Rice UV-damaged DNA binding protein homologues are most abundant in proliferating tissues. Ishibashi, T., Kimura, S., Yamamoto, T., Furukawa, T., Takata, K., Uchiyama, Y., Hashimoto, J., Sakaguchi, K. Gene (2003) [Pubmed]
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