Rev1 deficiency induces replication stress to cause metabolic dysfunction differently in males and females
Wietse In het Panhuis, Anastasia Tsaalbi‐Shtylik, Milena Schönke, Vanessa van Harmelen, Amanda C. M. Pronk, Trea C.M. Streefland, Hetty C. M. Sips, Salwa Afkir, Ko Willems van Dijk, Patrick C.N. Rensen, Niels de Wind, Sander Kooijman
Abstract
An increasing number of DNA lesions interferes with cellular replication leading to metabolic inflexibility. We utilized Rev1 knockout mice as a model for replication stress, and show a sex-dependent metabolic phenotype, with a pronounced reduction of lean mass and glucose tolerance. These data indicate that in obesity, we may end up in an infinite loop where metabolic disturbance promotes the formation of DNA lesions, which in turn interferes with cellular replication causing further metabolic disturbances.
Topics & Concepts
BiologyInternal medicineEndocrinologyDNA damageNAD+ kinaseDNA replicationGlycolysisAnaerobic glycolysisMetabolismDNABiochemistryEnzymeMedicineDNA Repair MechanismsPARP inhibition in cancer therapyMitochondrial Function and Pathology