Abstract:Structure-specific helicases, such as RecG, play an important role in the resolution of recombination intermediates. A bioinformatic analysis of mycobacterial genomes led to the identification of a protein (RecG ) with a C-terminal "edge" domain, similar to the wedge domain of RecG. RecG is predominately found in the phylum Actinobacteria and in few human pathogens. Mycobacterium smegmatis RecG was able to bind branched DNA structures in vitro but failed to interact with single- or double-stranded DNA. The exp… Show more
“…In this study, we demonstrate the role of mycobacterial RecG wed , a previously uncharacterized novel protein, in specifically binding to branched DNA structures including Holliday junctions. Our study suggests a probable role of RecG wed in the resolution of branched DNA structures and may contribute to the recombinational repair of DSBs, as well as restart of the stalled replication forks . …”
“…In this study, we demonstrate the role of mycobacterial RecG wed , a previously uncharacterized novel protein, in specifically binding to branched DNA structures including Holliday junctions. Our study suggests a probable role of RecG wed in the resolution of branched DNA structures and may contribute to the recombinational repair of DSBs, as well as restart of the stalled replication forks . …”
“…While MutM (Fpg) and MutY are involved in the cleavage of oxidized guanine and its paired base [20], UvrA (with UvrB) plays an essential role in DNA damage recognition and initiates nucleotide excision repair [17]. On the other hand, RecGwed has a binding affinity for branched DNA structures, mainly in the stationary phase [37], and is involved in drug resistance acquisition pathways of the L4.2.1 [45]. Considering the above, the presence of a more significant number of SNPs in these genes in drug resistant strains could indicate that they result of positive selection induced by anti-TB treatment, which confers advantages when facing the effects of the drugs.…”
Genes related to DNA damage repair in Mycobacterium tuberculosis are critical for survival and genomic diversification. The aim of this study is to compare the presence of SNPs in genes related to DNA damage repair in sensitive and drug-resistant M. tuberculosis genomes isolated from patients with and without type 2 diabetes mellitus (T2DM). We collected 399 M. tuberculosis L4 genomes from several public repositories; 224 genomes belonging to hosts without T2DM, of which 123 (54.9%) had drug sensitive tuberculosis (TB) and 101 (45.1%) had drug resistance (DR)-TB; and 175 genomes from individuals with T2DM, of which 100 (57.1%) had drug sensitive TB and 75 (42.9%) had DR-TB. The presence of SNPs in the coding regions of 65 genes related to DNA damage repair was analyzed and compared with the resistance profile and the presence/absence of T2DM in the host. The results show the phylogenetic relationships of some SNPS and L4 sub-lineages, as well as differences in the distribution of SNPs present in DNA damage repair-related genes related to the resistance profile of the infecting strain and the presence of T2DM in the host. Given these differences, it was possible to generate two discriminant functions to distinguish between drug sensitive and drug resistant genomes, as well as patients with or without T2DM.
The nicotinic/cholinergic antiinflammatory pathway plays integral roles in physiological and pathological regulation of inflammation. In this study, we tested the hypotheses that (i) nicotine guards against hemodynamic and renal vasoconstrictor dysfunction induced by endotoxemia in rats, and (ii) the α7‐nAChRs/heme oxygnase (HO) pathway constitutes a go‐between for the LPS‐nicotine interaction. Hemodynamic or renovascular functions were assessed 6 hr after i.p. administration of lipopolysaccharide (LPS, 5 mg/kg) with or without nicotine. LPS caused significant falls in systolic blood pressure (SBP) and reductions in cumulative renal vasoconstrictions induced by bolus injections of phenylephrine (PE, 0.002 – 4.42 nmol) or vasopressin (VP, 0.00092 – 0.27 nmol) into isolated perfused kidneys. LPS hypotension was demonstrated in both male and female rats, whereas the attenuation of renal vasoconstrictions was seen in male rats only. The reduced PE or VP responsiveness was reversed in preparations pretreated with nicotine (0.5, 1 and 2 mg/kg) in a dose‐dependent manner. This favorable action of nicotine disappeared after blockade of α7‐nAChRs (methyllycaconitine citrate, 2 mg/kg) or inhibition of HO‐1 (zinc protoporphyrin, 10 mg/kg). Moreover, the LPS attenuation of renal vasoconstrictions was improved upon concurrent treatment with pentoxfylline (TNFα inhibitor, 3 mg/kg), hemin (HO‐1 inducer, 10 mg/kg), tricarbonyldichlororuthenium (II) dimer (carbon monoxide‐releasing molecule, 10 mg/kg), in contrast to no effect for bilirubin (5 mg/kg). These data establish the first evidence that implicate the α7‐nAChRs/HO‐1/CO in the nicotine counteraction of renal vasoconstrictor hyporeactivity in endotoxemia.
Support or Funding Information
Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)
This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
