Bre1p-mediated histone H2B ubiquitylation regulates apoptosis in Saccharomyces cerevisiae.
BRE1 encodes an E3 ubiquitin protein ligase that is required for the ubiquitylation of histone H2B at lysine 123 (K123). Ubiquitylation of this histone residue is involved in a variety of cellular processes including gene activation and gene silencing. Abolishing histone H2B ubiquitylation also confers X-ray sensitivity and abrogates checkpoint activation after DNA damage. Here we show that Saccharomyces cerevisiae Bre1p exhibits anti-apoptotic activity in yeast and that this is linked to histone H2B ubiquitylation. We found that enhanced levels of Bre1p protect from hydrogen-peroxide-induced cell death, whereas deletion of BRE1 enhances cell death. Moreover, cells lacking Bre1p show reduced lifespan during chronological ageing, a physiological apoptotic condition in yeast. Importantly, the resistance against apoptosis is conferred by histone H2B ubiquitylation mediated by the E3 ligase activity of Bre1p. Furthermore, we found that the death of Deltabre1 cells depends on the yeast caspase Yca1p, because Deltabre1 cells exhibit increased caspase activity when compared with wild-type cells, and deletion of YCA1 leads to reduced apoptosis sensitivity of cells lacking Bre1p.
Walter
David
D
M. E. Müller Institute for Structural Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Matter
Anja
A
Fahrenkrog
Birthe
B
D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D054875:Ubiquitination
D051017:Apoptosis Regulatory Proteins; C472168:Bre1 protein, S cerevisiae; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D020169:Caspases; C456272:MCA1 protein, S cerevisiae