Lon protease previously has been shown to interact with DNA, but the role of this interaction for Lon proteolytic activity has not been characterized. In this study, we used truncated Lon constructs, bioinformatics analysis, and site-directed mutagenesis to identify Lon domains and residues crucial for Lon binding with DNA and effects on Lon proteolytic activity. We found that deletion of Lon's ATPase domain abrogated interactions with DNA. Substitution of positively charged amino acids in this domain in full-length Lon with residues conferring a net negative charge disrupted binding of Lon to DNA. These changes also affected the degradation of nucleic acid-binding protein substrates of Lon, intracellular localization of Lon, and cell morphology. tests revealed that Lon-DNA interactions are essential for Lon activity in cell division control. In summary, we demonstrate that the ability of Lon to bind DNA is determined by its ATPase domain, that this binding is required for processing protein substrates in nucleoprotein complexes, and that Lon may help regulate DNA replication in response to growth conditions.

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Most oxidative damage on mitochondrial DNA is corrected by the base excision repair (BER) pathway. However, the enzyme that catalyzes the rate-limiting reactiondeoxyribose phosphate (dRP) removalin the multienzymatic reaction pathway has not been completely determined in mitochondria. Also unclear is how a logical order of enzymatic reactions is ensured. Here, we present structural and enzymatic studies showing that human mitochondrial EXOG (hEXOG) exhibits strong 5′-dRP removal ability. We show that, unlike the canonical dRP lyases that act on a single substrate, hEXOG functions on a variety of abasic sites, including 5′-dRP, its oxidized product deoxyribonolactone (dL), and the stable synthetic analogue tetrahydrofuran (THF). We determined crystal structures of hEXOG complexed with a THF-containing DNA and with a partial gapped DNA to 2.9 and 2.1 Å resolutions, respectively. The structures illustrate that hEXOG uses a controlled 5′-exonuclease activity to cleave the third phosphodiester bond away from the 5′-abasic site. This study provides a structural basis for hEXOG’s broad spectrum of substrates. Further, we show that hEXOG can set the order of BER reactions by generating an ideal substrate for the subsequent reaction in BER and inhibit off-pathway reactions.

Stroke is still the leading cause of disability. Traveling stroke reduces the quality of life in the functional and psychological sphere. The European Stroke Initiative recommends that patients with stroke should be assured with rehabilitation as soon as possible. The most important goal of stroke rehabilitation is to restore all the functions lost by the patient as a result of the disease and also to compensate those which have been irretrievably lost. The latest data from the literature show that the best period in terms of potential for improvement of the functional status after stroke is the first three months of the onset of the stroke incident. To review the literature in the area of stroke rehabilitation and its importance for the improvement of the functional state.

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