In an advance, online publication of Nature this week, investigators at Yale University School of Medicine and their international colleagues report their use of whole-exome sequencing to identify "recessive WDR62 mutations in severe brain malformations," including microcephaly, pachygyria with cortical thickening, and hypoplasia of the corpus callosum. "In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones," the authors write, adding that WDR26 expression spans the period of embryonic neurogenesis and is primarily localized in the nucleus. They suggest that their study is another example of how whole-exome sequencing can be used "to identify disease loci in settings in which traditional methods have proved challenging."
A trio of researchers at the University of California, Davis, reports in Nature this week on the purification of the BRCA2 protein and "show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA." BRCA2, the authors write, targets RAD51 to single stranded DNA, "enabling RAD51 to displace replication protein-A from ssDNA and stabilizing RAD51–ssDNA filaments by blocking ATP hydrolysis." The authors suggest that their investigation reveals that BRCA2 is a "key mediator of homologous recombination."
Yale University School of Medicine's Ping Rao et al. this week show that "IκBβ acts to inhibit and activate gene expression during the inflammatory response." Specifically, in their in vivo analyses, Rao and colleagues found that "IκBβ degradation releases NF-κB dimers which upregulate pro-inflammatory target genes such as tumor necrosis factor-α," and that "IκBβ−/−mice are resistant to LPS-induced septic shock and collagen-induced arthritis." The authors suggest that "blocking IκBβ might be a promising new strategy for selectively inhibiting ... TNF-α production during the inflammatory response."
Investigators in Europe describe "somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes" in this week's Nature Genetics. Because deletions of chromosome 7 or 7q are associated with poor prognosis, the team set out to investigate relevant genes. They found that "EZH2, located at 7q36.1, is frequently targeted in MDS." Their subsequent analyses suggest that the gene is a tumor suppressor.