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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Su, Xue Bessie Pillus, Lorraine |
| Description | Author Affiliation: Su XB ( Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0347); Pillus L ( Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0347); |
| Abstract | Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of -ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 11 |
| Volume Number | 113 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2016-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glutamate Dehydrogenase (NADP+) Metabolism Heterochromatin Saccharomyces Cerevisiae Proteins Telomere Genetics Amino Acid Sequence Computer Simulation Gene Silencing Histones Jumonji Domain-Containing Histone Demethylases Ketoglutaric Acids Molecular Sequence Data Silent Information Regulator Proteins, Saccharomyces Cerevisiae Sirtuin 2 Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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