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PLOS Papers on FANCJ in Cancer, Host Factors Influencing Wound Microbiome, RapidRat

In PLOS Genetics, researchers from the University of Zurich and New York University School of Medicine explore previously reported ties between cancer and mutations in the iron-sulfur (FeS) domain of the Fancomi anemia-related, DNA helicase enzyme-coding gene FANCJ. In a series of site-directed mutagenesis, cell line experiments, assays, and more, the team found that the mutations in the FeS domain alter the enzyme's G-quadruplex, or G4, metabolism, apparently leading to enhanced sensitivity to drugs that stabilize these G4 structures, including a small molecule called CX-5461 being tested in early stage trials of individuals with BRCA-mutated tumors. Based on their findings, the authors suggest that the protein typically "resolves G4 structures in the context of the replisome to allow replication through guanine-rich regions of the genome," while alterations that significantly impact helicase activity or iron-sulfur co-factor binding by FANCJ "are sufficient to render cells more sensitive to CX-5461 treatment."

A Texas Tech University-led team shares findings from a genome-wide association study aimed at uncovering host genetic factors influencing the microbial communities found at chronic wound sites for a paper appearing in PLOS Pathogens. By bringing together host genotyping profiles and 16S ribosomal RNA sequencing data from wound samples in dozens of individuals treated for chronic wounds, the researchers identified and attempted to validate eight wound microbiome candidate SNPs. In particular, they flagged host variants in the TLN2 and ZNF521 genes that appeared to influence the representation by Pseudomonas aeruginosa and Staphylococcus epidermidis pathogens in the wound microbiome, along with SNPs at half a dozen loci with ties to wound microbiome diversity features that can influence wound healing.

Researchers from the University of British Columbia and Parks Canada report in PLOS One on a genotyping-by-sequencing-based strategy dubbed RapidRat for finding traces of invasive brown (Rattus norvegicus) and black (R. rattus) rat species on the Haida Gwaii islands off of the British Columbia coast. Using primers targeting hundreds of variable rat loci, the team came up with a genotyping-in-thousands by sequencing, or GT-seq, panel for genotyping brown and black rats on the islands of Agglomerate, Hotspring, and Ramsay and teasing apart rat population structures at these sites — an approach that appeared to compare favorably with prior double-digest restriction-site associated DNA sequencing. "Overall, we demonstrated that RapidRat is an effective tool for managing invasive rat populations in Haida Gwaii," the authors note, "and provided a clear framework for GT-seq panel development for informing biodiversity conservation in other systems."