NIA Inter-Lab Project: Analyses of Age-Related Phenotypes Displayed by RECQL1 Deficiency in a Rodent Model

National Institute On Aging

Investigators

Abstract

The molecular pathologies caused by RecQ helicase deficiency are particularly difficult to characterize because five human RecQ homologs with partially overlapping functions exist. RECQL1 is the most abundant of the human RecQ helicases and has critical roles in genomic stability. We will characterize a defined RECQ1 knockout mouse model subjected to conditions of dietary manipulation or replicative stress. The in vivo mouse studies will elucidate novel phenotypes of RECQL1 deficiency under conditions of dietary or environmental stress. Dysfunction as a consequence of RECQL1 loss will be most prevalent in tissues and organs characterized by rapidly dividing cells that experience the greatest burden of replicative lesions. This NIA inter-lab project will provide a foundation for new research directions in the dietary and DNA damage response fields that are of great relevance to mammalian aging.