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

Esti Singer, Yardena B.H. Silas, Sigal Ben-Yehuda, Ophry Pines*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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 fumarasedependent 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.

Original languageAmerican English
Article numbere30927
StatePublished - 15 Nov 2017

Bibliographical note

Funding Information:
CREATE Project of the Na tional Research Foundation of Singapore

Funding Information:
Israel Science Foundation Ophry Pines German Israeli Project Cooperation Ophry Pines CREATE Project of the National Research Foundation of Singapore Ophry Pines.

Publisher Copyright:
© Singer et al.


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