These ‘master’ proteins protect us from deadly mutations — and could inspire new drugs

Our genomes are full of mutations that have the potential to damage our health or even kill us. Yet most of them rarely cause problems. Why? These powerful tools reveal the ‘control knobs’ of the genome It’s partly thanks to a family of proteins that mask, or ‘buffer’, the ill effects that these mutations would otherwise unleash. This buffering might help to explain why gene variants cause disease in some people but seem to have limited or no impact on others. It could also underlie how some cancer cells and pathogens threaten their hosts and evade drugs. And it enables genetic variation to accumulate in populations, providing a potential resource for future evolution. Researchers have known for decades that one of the most important factors in mutational buffering is a protein called HSP90 and its family of other HSP proteins. Now, biologists are examining the roles of these proteins in more detail than they ever could before, owing to advances in techniques such as cell screening and genetic editing , as well as the availability of large genomic data sets and extensive health records. Advances in the past two decades or so have “shifted our view on HSP90 buffering as a theoretical idea to one with immediate and important practical applications, especially in the clinic”, says geneticist Georgios Karras at the University of Texas MD Anderson Cancer Center in Houston. HSP90, for instance, might mediate the risks of breast cancer linked to the BRCA1 gene in some individuals. …