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Gene Review

TOPBP1  -  topoisomerase (DNA) II binding protein 1

Homo sapiens

Synonyms: DNA topoisomerase 2-binding protein 1, DNA topoisomerase II-beta-binding protein 1, DNA topoisomerase II-binding protein 1, KIAA0259, TOP2BP1, ...
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Disease relevance of TOPBP1


High impact information on TOPBP1


Biological context of TOPBP1

  • TopBP1 contains eight BRCT (BRCA1 carboxyl-terminal) motifs and upon DNA damage is recruited to stalled replication forks, where it participates in a DNA damage checkpoint [8].
  • Through this interaction, TopBP1 repressed multiple activities of E2F1, including transcriptional activity, induction of S-phase entry, and apoptosis [8].
  • Our data suggest a model in which UV irradiation-induced DNA damage depends, at least in part, on the accumulation of the E2F4 transcription factor on the MCM10 and TopBP1 promoters, which results in suppression of DNA replication [1].
  • Furthermore, Xenopus egg extracts containing a version of TopBP1 with an inactivating point mutation in the ATR-activating domain are defective in checkpoint regulation [6].
  • Phosphorylation by Akt induces oligomerization of TopBP1 through its seventh and eighth BRCT domains [9].

Associations of TOPBP1 with chemical compounds


Physical interactions of TOPBP1


Co-localisations of TOPBP1


Regulatory relationships of TOPBP1

  • Together, our findings demonstrate that PML regulates TopBP1 functions by association and stabilization of the protein in response to IR-induced DNA damage [10].
  • Finally, we show that TopBP1 is required for the DNA damage-induced interaction between Claspin and Chk1 [14].

Other interactions of TOPBP1


  1. Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor. Yoshida, K., Inoue, I. Oncogene (2004) [Pubmed]
  2. Altered gene expression pattern in cultured human breast cancer cells treated with hepatocyte growth factor/scatter factor in the setting of DNA damage. Yuan, R., Fan, S., Achary, M., Stewart, D.M., Goldberg, I.D., Rosen, E.M. Cancer Res. (2001) [Pubmed]
  3. Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer. Karppinen, S.M., Erkko, H., Reini, K., Pospiech, H., Heikkinen, K., Rapakko, K., Syv??oja, J.E., Winqvist, R. Eur. J. Cancer (2006) [Pubmed]
  4. TopBP1 contains a transcriptional activation domain suppressed by two adjacent BRCT domains. Wright, R.H., Dornan, E.S., Donaldson, M.M., Morgan, I.M. Biochem. J. (2006) [Pubmed]
  5. TOPping up ATR activity. Bartek, J., Mailand, N. Cell (2006) [Pubmed]
  6. TopBP1 activates the ATR-ATRIP complex. Kumagai, A., Lee, J., Yoo, H.Y., Dunphy, W.G. Cell (2006) [Pubmed]
  7. TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Liu, K., Luo, Y., Lin, F.T., Lin, W.C. Genes Dev. (2004) [Pubmed]
  8. Regulation of E2F1 by BRCT domain-containing protein TopBP1. Liu, K., Lin, F.T., Ruppert, J.M., Lin, W.C. Mol. Cell. Biol. (2003) [Pubmed]
  9. Regulation of TopBP1 oligomerization by Akt/PKB for cell survival. Liu, K., Paik, J.C., Wang, B., Lin, F.T., Lin, W.C. EMBO J. (2006) [Pubmed]
  10. PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Xu, Z.X., Timanova-Atanasova, A., Zhao, R.X., Chang, K.S. Mol. Cell. Biol. (2003) [Pubmed]
  11. Human TopBP1 ensures genome integrity during normal S phase. Kim, J.E., McAvoy, S.A., Smith, D.I., Chen, J. Mol. Cell. Biol. (2005) [Pubmed]
  12. Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response. Honda, Y., Tojo, M., Matsuzaki, K., Anan, T., Matsumoto, M., Ando, M., Saya, H., Nakao, M. J. Biol. Chem. (2002) [Pubmed]
  13. The transcription factor Egr-1 is a regulator of the human TopBP1 gene. Usskilat, C., Skerka, C., Saluz, H.P., Hänel, F. Gene (2006) [Pubmed]
  14. Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation. Liu, S., Bekker-Jensen, S., Mailand, N., Lukas, C., Bartek, J., Lukas, J. Mol. Cell. Biol. (2006) [Pubmed]
  15. A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. Yamane, K., Wu, X., Chen, J. Mol. Cell. Biol. (2002) [Pubmed]
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