Premium
Rad53p Activation Alters Chromatin Structure, Induces Respiration and Elevates Cellular ATP Level
Author(s) -
Bu Pengli,
Shah Ankita,
Zeng Joey,
Bhagwat Madhura S.,
Nagar Shreya,
Vancura Ales
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.523.11
Subject(s) - chromatin , oxidative phosphorylation , dna damage , citric acid cycle , histone , biology , microbiology and biotechnology , dna , mitochondrial dna , mitochondrion , biochemistry , chemistry , gene , enzyme
Rad53p is an essential kinase in the DNA damage response in Saccharomyces cerevisiae . Here we show that activation of Rad53p, either via genetic manipulation or by treatment with genotoxic chemicals, induces mitochondrial respiration. Activation of Rad53p results in reduced transcription of histone genes and globally decreased DNA nucleosome occupancy. This globally altered chromatin structure leads to increased expression of genes encoding enzymes of tricarboxylic acid cycle (TCA), electron transport chain (ETC), and oxidative phosphorylation (OXPHOS) and increased mitochondrial DNA (mtDNA) copy number, oxygen consumption, and ATP synthesis. These findings are surprising and counterintuitive, since it is widely believed that DNA damage results in downregulation of oxidative metabolism to protect DNA from the effects of reactive oxygen species, produced during ETC and OXPHOS. However, our results indicate that the elevated ATP synthesis improves cell survival under conditions of DNA damage and Rad53p activation. In summary, our study reveals a novel role for Rad53p activation in the restructuring of global nucleosomal chromatin architecture and concomitant metabolic transition from fermentation to respiration. Support or Funding Information Supported by NIH GM120710 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .