E3 ubiquitin ligase; forms heterodimer with Rad6p to regulate K63 polyubiquitination in response to oxidative stress and to monoubiquinate histone H2B-K123, which is required for the subsequent methylation of histone H3-K4 and H3-K79; required for DSBR, transcription, silencing, and checkpoint control; interacts with RNA-binding protein Npl3p, linking histone ubiquitination to mRNA processing; Bre1p-dependent histone ubiquitination promotes pre-mRNA splicing