In a paper published online in advance in Nature this week, a team led by investigators at Vanderbilt University presents the crystal structures of "Bacillus cereus AlkD glycosylase in complex with DNAs containing alkylated, mismatched, and abasic nucleotides," which they suggest may elucidate "an unprecedented nucleic acid capture mechanism for [the] excision of DNA damage." AlkD is a unique glycosylase in that it "captures the extrahelical lesion in a solvent-exposed orientation, providing an illustration for how hydrolysis of N3- and N7-alkylated bases may be facilitated by increased lifetime out of the DNA helix," the authors write.
A multi-institution research team based in Cleveland reports online in Nature this week that "oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands." Specifically, the team shows that TLR2 recognizes the molecular patterns of carboxyalkylpyrroles, whereas TLR4 does not, which leads to an angiogenic response independent of vascular endothelial growth factors. The team performed "neutralization of endogenous carboxyalkylpyrroles" and found that it "impaired wound healing and tissue re-vascularization and diminished tumor angiogenesis," they write.
Researchers at the Memorial Sloan-Kettering Cancer Center and their colleagues show that ETV1, which is highly expressed in interstitial cells of Cajal sensitive to oncogenic KIT-mediated transformation, is a lineage survival factor in gastrointestinal stromal tumors. The team performed transcriptome profiling and global analyses of ETV1-binding sites; their data suggest that "ETV1 is a master regulator of an ICC-GIST-specific transcription network mainly through enhancer binding," the authors write.
And in a paper published online in advance in Nature Genetics, researchers report their re-sequencing of 200 human exomes from individuals from Denmark via "targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold." The team found 121,870 SNPs, including more than 53,000 coding SNPs in these individuals. "We identified a 1.8-fold excess of deleterious, non-synonymous cSNPs over synonymous cSNPs in the low-frequency range," the authors write, adding that the "excess was more pronounced for X-linked SNPs" and therefore suggestive that "deleterious substitutions are primarily recessive."