Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1.

ABSTRACT: The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to double-strand DNA breaks, whereas the related kinase ATR leads a parallel signaling cascade that is activated by replication stress. To dissect the physiological relationship between the ATM and ATR pathways, we generated mice defective for both. Because complete ATR pathway inactivation causes embryonic lethality, we weakened the ATR mechanism to different degrees by impairing HUS1, a member of the 911 complex that is required for efficient ATR signaling. Notably, simultaneous AT

SUBMITTER: Balmus G 

PROVIDER: S-EPMC3392115 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature