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Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis.

Title: Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis.
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Name(s): Singh, Rakesh Kumar, author
Kabbaj, Marie-Helene Miquel, author
Paik, Johanna, author
Gunjan, Akash, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2009-08-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Histone levels are tightly regulated to prevent harmful effects such as genomic instability and hypersensitivity to DNA-damaging agents due to the accumulation of these highly basic proteins when DNA replication slows down or stops. Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in Saccharomyces cerevisiae. Here we demonstrate that excess histones associate with Rad53 in vivo and seem to undergo modifications such as tyrosine phosphorylation and polyubiquitylation, before their proteolysis by the proteasome. We have identified the Tyr 99 residue of histone H3 as being critical for the efficient ubiquitylation and degradation of this histone. We have also identified the ubiquitin conjugating enzymes (E2) Ubc4 and Ubc5, as well as the ubiquitin ligase (E3) Tom1 (temperature dependent organization in mitotic nucleus 1), as enzymes involved in the ubiquitylation of excess histones. Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA.
Identifier: FSU_pmch_19578373 (IID), 10.1038/ncb1903 (DOI), PMC2720428 (PMCID), 19578373 (RID), 19578373 (EID), ncb1903 (PII)
Grant Number: R15 GM079678, R15 GM079678-01, R15GM079678-01
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720428.
Subject(s): Blotting, Western
Cell Cycle Proteins/genetics
Cell Cycle Proteins/metabolism
Checkpoint Kinase 2
Chromatin Assembly Factor-1
Chromosomal Proteins, Non-Histone/genetics
Chromosomal Proteins, Non-Histone/metabolism
DNA-Binding Proteins/genetics
DNA-Binding Proteins/metabolism
Histones/genetics
Histones/metabolism
Hydrolysis
Immunoprecipitation
Molecular Chaperones/genetics
Molecular Chaperones/metabolism
Mutation
Phosphorylation
Proteasome Endopeptidase Complex/metabolism
Protein Binding
Protein-Serine-Threonine Kinases/genetics
Protein-Serine-Threonine Kinases/metabolism
Saccharomyces cerevisiae/genetics
Saccharomyces cerevisiae/metabolism
Saccharomyces cerevisiae Proteins/genetics
Saccharomyces cerevisiae Proteins/metabolism
Tyrosine/metabolism
Ubiquitin-Conjugating Enzymes/genetics
Ubiquitin-Conjugating Enzymes/metabolism
Ubiquitin-Protein Ligases/genetics
Ubiquitin-Protein Ligases/metabolism
Ubiquitination
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_19578373
Owner Institution: FSU
Is Part Of: Nature cell biology.
1476-4679
Issue: iss. 8, vol. 11

Choose the citation style.
Singh, R. K., Kabbaj, M. -H. M., Paik, J., & Gunjan, A. (2009). Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis. Nature Cell Biology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_19578373