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Gene Review:

BRE1 - E3 ubiquitin-protein ligase BRE1

Saccharomyces cerevisiae S288c

Synonyms: Brefeldin A-sensitivity protein 1, YDL074C

Wood, A. et al., Yamashita, K. et al., Giannattasio, M. et al., Daniel, J.A. et al., Wood, A. et al., et al.

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High impact information on BRE1

Bre1 is essential for this recruitment of Rad6 and is dedicated to the transcriptional pathway of Rad6 [1].
The RING finger of Bre1 is required for ubiquitination of histone H2B, methylation of lysine 4 and 79 of H3 and for telomeric silencing [1].
These results suggest that Bre1 is the likely E3 enzyme that directs Rad6 to modify chromatin and ultimately to affect gene expression [1].
The Arabidopsis thaliana Homolog of Yeast BRE1 Has a Function in Cell Cycle Regulation during Early Leaf and Root Growth [2].
These results suggest that Rad6-Bre1, through ubiquitylation of histone H2B, is necessary for efficient recruitment and/or stabilization of a DSB-forming machinery containing Spo11 [3].

Biological context of BRE1

Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis [3].
Microarray experiments also confirmed that the pattern of gene expression changes seen in cells lacking Lge1p, Bre1p, or Rad6p or containing the H2B-K123R mutant as the only form of H2B share some overlap but are distinct [4].
Given the requirement of Rad6/Bre1-dependent ubiquitination of histone H2B for H3 dimethylation (at lysines 4 and 79) and gene silencing (2-7), removal of ubiquitin from H2B may have a significant regulatory effect on transcription [5].
The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1 [6].

Other interactions of BRE1

We demonstrate that ubiquitination of histone H2B on lysine 123 by the Rad6-Bre1 complex, is necessary for activation of Rad53 kinase and cell cycle arrest [6].
Thus, in addition to its role during the elongation phase of transcription, the Paf1 complex appears to activate the function but not the placement of the Rad6-Bre1 ubiquitin-protein ligase at the promoters of active genes [7].

Analytical, diagnostic and therapeutic context of BRE1

Chromatin immunoprecipitation experiments indicated that both Rad6 and Bre1 are recruited to a promoter [1].

References

Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Wood, A., Krogan, N.J., Dover, J., Schneider, J., Heidt, J., Boateng, M.A., Dean, K., Golshani, A., Zhang, Y., Greenblatt, J.F., Johnston, M., Shilatifard, A. Mol. Cell (2003) [Pubmed]
The Arabidopsis thaliana Homolog of Yeast BRE1 Has a Function in Cell Cycle Regulation during Early Leaf and Root Growth. Fleury, D., Himanen, K., Cnops, G., Nelissen, H., Boccardi, T.M., Maere, S., Beemster, G.T., Neyt, P., Anami, S., Robles, P., Micol, J.L., Inzé, D., Van Lijsebettens, M. Plant Cell (2007) [Pubmed]
Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Yamashita, K., Shinohara, M., Shinohara, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination. Zhang, X., Kolaczkowska, A., Devaux, F., Panwar, S.L., Hallstrom, T.C., Jacq, C., Moye-Rowley, W.S. J. Biol. Chem. (2005) [Pubmed]
Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription. Daniel, J.A., Torok, M.S., Sun, Z.W., Schieltz, D., Allis, C.D., Yates, J.R., Grant, P.A. J. Biol. Chem. (2004) [Pubmed]
The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. Giannattasio, M., Lazzaro, F., Plevani, P., Muzi-Falconi, M. J. Biol. Chem. (2005) [Pubmed]
The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p. Wood, A., Schneider, J., Dover, J., Johnston, M., Shilatifard, A. J. Biol. Chem. (2003) [Pubmed]

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AGOS_AER074W	Ashbya gossypii ATCC 10895
KLLA0B02981g	Kluyveromyces lactis NRRL Y-1140

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