期刊
CELL
卷 154, 期 5, 页码 983-995出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.07.028
关键词
-
资金
- Cancer Research UK
- European Research Council
- Cancer Research UK [11567] Funding Source: researchfish
DNA damage triggers polyubiquitylation and degradation of the largest subunit of RNA polymerase II (RNAPII), a mechanism of last resort employed during transcription stress. In yeast, this process is dependent on Def1 through a previously unresolved mechanism. Here, we report that Def1 becomes activated through ubiquitylation- and proteasome-dependent processing. Def1 processing results in the removal of a domain promoting cytoplasmic localization, resulting in nuclear accumulation of the clipped protein. Nuclear Def1 then binds RNAPII, utilizing a ubiquitin-binding domain to recruit the Elongin-Cullin E3 ligase complex via a ubiquitin-homology domain in the Ela1 protein. This facilitates polyubiquitylation of Rpb1, triggering its protea-some-mediated degradation. Together, these results outline the multistep mechanism of Rpb1 polyubiquitylation triggered by transcription stress and uncover the key role played by Def1 as a facilitator of Elongin-Cullin ubiquitin ligase function.
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