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

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Abstract

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 Bacillus subtilis (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 B. subtilis 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.

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Esti Singer

Department of Microbiology and Molecular Genetics, Hebrew University, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Yardena BH Silas

Department of Microbiology and Molecular Genetics, Hebrew University, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Sigal Ben-Yehuda

Department of Microbiology and Molecular Genetics, Hebrew University, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Ophry Pines

Department of Microbiology and Molecular Genetics, Hebrew University, Jerusalem, Israel

For correspondence
ophryp@ekmd.huji.ac.il

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7126-2575

Funding

Israel Science Foundation

Ophry Pines

German Israeli Project Cooperation

Ophry Pines

CREATE Project of the National Research Foundation of Singapore

Ophry Pines

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.