In this new study, researchers from the Wellcome Sanger Institute, and their collaborators at the UK Dementia Research Institute at the University of Cambridge, set out to better understand the biology of cellular health and identify genes key to maintaining genome stability. Using a set of genetically modified mouse lines, the team identified 145 genes that play key roles in either increasing or decreasing the formation of abnormal micronuclei structures2. The most dramatic increases in genomic instability were seen when the researchers knocked out the gene DSCC1, increasing abnormal micronuclei formation five-fold. Using CRISPR screening, researchers showed this effect triggered by DSCC1 loss could be partially reversed through inhibiting protein SIRT14.

 

Professor Gabriel Balmus, senior author of the study at the UK Dementia Research Institute at the University of Cambridge, formerly at the Wellcome Sanger Institute, said: "Continued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causes, with the goal of improving outcomes and the overall quality of life for individuals across various conditions. Our study underscores the potential of SIRT inhibitors as a therapeutic pathway for cohesinopathies and other genomic disorders. It suggests that early intervention, specifically targeting SIRT1, could help mitigate the biological changes linked to genomic instability before they progress."