In PNAS this week, a team of US researchers present a study on the conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops. MSH2/MSH3 discriminates between repair-competent and repair-resistant loops by "sensing the conformational dynamics of their junctions," the authors write. MSH2/MSH3 dissociates from repair-competent loops, but repair-resistant CAG loops trap nucleotide-bound MSH2/MSH3 and don't allow it to dissociate from DNA. "We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation," the team adds.
Also in PNAS, researchers in Switzerland say that PI3Kγ negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance, within a non-hematopoietic cell type. In this study, the team shows that protection from insulin resistance, metabolic inflammation, and fatty liver in mice lacking functional PI3Kγ is largely due to their leaner phenotype. "Furthermore," the team adds, "our data show that PI3Kγ action on diet-induced obesity depends on PI3Kγ activity within a nonhematopoietic compartment, where it promotes energetic efficiency for fat mass gain." These results suggest that PI3Kγ could be a drug target for treating obesity.
In the PNAS Early Edition , researchers in Japan report the main auxin biosynthesis pathway in Arabidopsis. The team writes that the tryptophan aminotransferase of Arabidopsis protein family produces indole-3-pyruvic acid, and that the yucca flavin monooxygenase-like proteins function to convert indole-3-pyruvic acid into indole-3-acetic acid in Arabidopsis. "We further show that YUC protein expressed in Escherichia coli directly converts IPA to IAA. Indole-3-acetaldehyde is probably not a precursor of IAA in the IPA pathway," the authors write. "Our results indicate that YUC proteins catalyze a rate-limiting step of the IPA pathway, which is the main IAA biosynthesis pathway in Arabidopsis."
Also in the online edition, a team of researchers from the US and Canada reports the molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. The team sequenced the genomes of eight S. aureus clinical isolates representative of the phage-type 80/81 clone, an MRSA clone, and contemporary S. aureus clones, and found that there was "coincident divergence of these clones from a recent common ancestor, a finding that resolves controversy about the evolutionary history of the lineage." The researchers also found nonsynonymous SNPs in genes encoding accessory gene regulator C and α-hemolysin. "We conclude that agr and hla (along with penicillin resistance) were essential for world dominance of phage-type 80/81 S. aureus, whereas key SNPs in contemporary CC30 clones restrict these pathogens to hospital settings in which the host is typically compromised," the authors add.