- February 18, 2021
Bacterial fumarase and L-malic acid are evolutionary ancient components of the DNA damage response
Esti Singer, Yardena BH Silas, Sigal Ben-Yehuda, Ophry Pines|Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University, Jerusalem, Israel, CREATE-NUS-HUJ Program and the Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore|2017|eLife|6: e30927 https://doi.org/10.7554/eLife.30927
Fumarase is a conserved moonlighting (duel targeting) protein, where it performs functions in the tricarboxylic acid cycle in mitochondria and participates in the DNA damage response in the nucleus in eukaryotes. It was previously demonstrated that majority of dual targeting proteins have discrete functions in the different subcellular compartments, regardless of their dual-targeting mechanism. In this study, prokaryotic fumarase was implicated in the DNA damage response and fumarase enzymatic activity was monitored by RT-qPCR on the Mic qPCR Cycler using relative quantification methods. It was shown that bacteria grown with DNA-damaging chemical have increases levels of fumarase and co-localises with the bacterial DNA. This in turn affects the production of a protein called RecN, which triggers DNA repair, via L-malic acid. These findings suggest that that the dual function of fumarase preceded the dual targeting that we find in eukaryotes as all reactions take place inside the main space within the cell.