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Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.

Title: Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.
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Name(s): Singh, Rakesh Kumar, author
Gonzalez, Melanie, author
Kabbaj, Marie-Helene Miquel, author
Gunjan, Akash, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2012-01-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus) domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene) finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs) YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases) respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3 ubiquitin ligases to ensure excess histone degradation and thus contribute to the maintenance of genomic stability.
Identifier: FSU_pmch_22570702 (IID), 10.1371/journal.pone.0036295 (DOI), PMC3343073 (PMCID), 22570702 (RID), 22570702 (EID), PONE-D-11-24652 (PII)
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343073.
Subject(s): Antineoplastic Agents/pharmacology
Antineoplastic Agents/toxicity
Cell Cycle Proteins/metabolism
Gene Expression
Histones/genetics
Histones/metabolism
Hydroxyurea/pharmacology
Hydroxyurea/toxicity
Molecular Chaperones/metabolism
Mutation
Protein Binding
RING Finger Domains/genetics
Saccharomyces cerevisiae/enzymology
Saccharomyces cerevisiae/genetics
Saccharomyces cerevisiae Proteins/genetics
Saccharomyces cerevisiae Proteins/metabolism
Ubiquitin-Conjugating Enzymes/metabolism
Ubiquitin-Protein Ligases/genetics
Ubiquitin-Protein Ligases/metabolism
Ubiquitination
Vesicular Transport Proteins/genetics
Vesicular Transport Proteins/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_22570702
Owner Institution: FSU
Is Part Of: PloS one.
1932-6203
Issue: iss. 5, vol. 7

Choose the citation style.
Singh, R. K., Gonzalez, M., Kabbaj, M. -H. M., & Gunjan, A. (2012). Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae. Plos One. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_22570702