Nitrosative stress suppresses checkpoint activation after DNA synthesis inhibition.

ABSTRACT: DNA synthesis is promoted by the dephosphorylation and activation of cyclin-dependent kinase 2 (Cdk2) complexes by Cdc25A. Nitrosative stress suppresses Cdk2 dephosphorylation by Cdc25A in vitro and inhibits Cdc25A protein translation in cells, but the effects on S-phase progression remain unexamined. Herein we report that nitrosative stress catalyzed by inducible nitric oxide (*NO) synthase (iNOS) or the chemical nitrosant S-nitrosocysteine ethyl ester (SNCEE) rapidly inhibited DNA synthesis concomitant with Cdc25A loss. Surprisingly, this inhibition of DNA synthesis was refractory to ectopic expression of Cdc25A or a Cdc25-independent Cdk2 mutant. Nitrosative stress inhibited DNA synthesis without activating checkpoint signaling, thus distinguishing it from S-phase arrest mediated by oth

SUBMITTER: Tomko RJ 

PROVIDER: S-EPMC2752830 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature