In metazoans, accurate replication of chromosomes is ensured by the coupling of DNA synthesis to the synthesis of histone proteins. Expression of replication-dependent histone genes is restricted to S-phase by a combination of cell cycle-regulated transcriptional and post-transcriptional control mechanisms and is linked to DNA replication by a poorly understood mechanism involving checkpoint kinases [Su, Gao, Schneider, Helt, Weiss, O'Reilly, Bohmann and Zhao (2004) EMBO J. 23, 1133–1143; Kaygun and Marzluff (2005) Nat. Struct. Mol. Biol. 12, 794–800]. Here we propose a model for the molecular mechanisms that link these two important processes within S-phase, and propose roles for multiple checkpoints in this mechanism.
- ataxia-telangiectasia mutated gene (ATM)
- ataxia-telangiectasia and Rad3-related (ATR)
- DNA-activated protein kinase
- DNA replication
- histone gene expression
- human phosphatidylinositol 3-kinase-related kinase
- RNA stability