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.

富马酶分布在真核细胞的两个区室之间。该酶催化线粒体中富马酸向L-苹果酸的可逆转化，这是三羧酸（TCA）循环的一部分，而在胞质/细胞核中则是DNA损伤反应（DDR）的一部分。在这里，我们显示了原核生物枯草芽孢杆菌（Fum-bc）模型的富马酸酯在DNA损伤后被诱导，与细菌DNA共定位，并且是DDR必需的。Fum-bc可以替代酵母中的两种真核功能。此外，我们发现枯草芽孢杆菌依赖富马酸酶的细胞内信号转导DDR通过产生L-苹果酸来实现，这会影响RecN的翻译，RecN是第一个被募集到DNA损伤位点的蛋白质。这项研究提供了一种不同的进化方案，其中古老的原核富马酶的双重功能导致其随后分布到真核生物的不同细胞区室中。