Linked Life Data

21673141

Source:http://linkedlifedata.com/resource/pubmed/id/21673141

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2011-6-29
pubmed:abstractText
Recent work has identified several posttranslational modifications (PTMs) on chromatin-remodeling complexes. Compared with our understanding of histone PTMs, significantly less is known about the functions of PTMs on remodeling complexes, because identification of their specific roles often is hindered by the presence of redundant pathways. Remodels the Structure of Chromatin (RSC) is an essential, multifunctional ATP-dependent chromatin-remodeling enzyme of Saccharomyces cerevisiae that preferentially binds acetylated nucleosomes. RSC is itself acetylated by Gcn5 on lysine 25 (K25) of its Rsc4 subunit, adjacent to two tandem bromodomains. It has been shown that an intramolecular interaction between the acetylation mark and the proximal bromodomain inhibits binding of the second bromodomain to acetylated histone H3 tails. We report here that acetylation does not significantly alter the catalytic activity of RSC or its ability to recognize histone H3-acetylated nucleosomes preferentially in vitro. However, we find that Rsc4 acetylation is crucial for resistance to DNA damage in vivo. Epistatic miniarray profiling of the rsc4-K25R mutant reveals an interaction with mutants in the INO80 complex, a mediator of DNA damage and replication stress tolerance. In the absence of a core INO80 subunit, rsc4-K25R mutants display sensitivity to hydroxyurea and delayed S-phase progression under DNA damage. Thus, Rsc4 helps promote resistance to replication stress, and its single acetylation mark regulates this function. These studies offer an example of acetylation of a chromatin-remodeling enzyme controlling a biological output of the system rather than regulating its core enzymatic properties.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10620-5
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress.
pubmed:affiliation
Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94158, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural