Bacterial fumarase and L-malic acid are evolutionary ancient components of the DNA damage response

• Published in: eLife Vol. 6
• Main Authors: Singer, Esti, Silas, Yardena Bh, Ben-Yehuda, Sigal, Pines, Ophry
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 15.11.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Analysis; Bacillus subtilis - enzymology; Bacteria; Bacterial genetics; Bacterial Proteins - metabolism; Cell Biology; Cytosol; Deoxyribonucleic acid; DNA; DNA Damage; DNA damage response; DNA repair; DNA Restriction Enzymes - metabolism; DNA, Bacterial - metabolism; double strand break; Enzymes; Fumarase; Fumarate Hydratase - metabolism; Fumaric acid; Gene expression; Genes; Genetic code; Genetic Complementation Test; Genetic research; Intracellular signalling; Ionizing radiation; Kinases; L- Malic acid; Localization; Malates - metabolism; Malic acid; metabolite signaling; Mitochondria; Nuclei; Physiological aspects; Plants (Organisms); Protein Binding; Proteins; Radiation (Physics); RecN; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Statistical analysis; Tricarboxylic acid cycle; Yeast; B. subtilis; L- Malic acid; cell biology; DNA damage response; double strand break; RecN; metabolite signaling; fumarase
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.30927

Fumarase is distributed between two compartments of the eukaryotic cell. The enzyme catalyses the reversible conversion of fumaric to L-malic acid in mitochondria as part of the tricarboxylic acid (TCA) cycle, and in the cytosol/nucleus as part of the DNA damage response (DDR). Here, we show that fumarase of the model prokaryote (Fum-bc) is induced upon DNA damage, co-localized with the bacterial DNA and is required for the DDR. Fum-bc can substitute for both eukaryotic functions in yeast. Furthermore, we found that the fumarase-dependent intracellular signaling of the DDR is achieved via production of L-malic acid, which affects the translation of RecN, the first protein recruited to DNA damage sites. This study provides a different evolutionary scenario in which the dual function of the ancient prokaryotic fumarase, led to its subsequent distribution into different cellular compartments in eukaryotes.