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. 2005 Sep;12(9):794-800.
doi: 10.1038/nsmb972. Epub 2005 Aug 7.

Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1

Handan Kaygun  1 , William F Marzluff
Affiliations

Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1

Handan Kaygun et al. Nat Struct Mol Biol. 2005 Sep.

Abstract

Eukaryotic cells coordinately regulate histone and DNA synthesis. In mammalian cells, most of the regulation of histone synthesis occurs post-transcriptionally by regulating the concentrations of histone mRNA. As cells enter S phase, histone mRNA levels increase, and at the end of S phase they are rapidly degraded. Moreover, inhibition of DNA synthesis causes rapid degradation of histone mRNAs. Replication-dependent histone mRNAs are the only metazoan mRNAs that are not polyadenylated. Instead, they end with a conserved stem-loop structure, which is the only cis-acting element required for coupling regulation of histone mRNA half-life with DNA synthesis. Here we show that regulated degradation of histone mRNAs requires Upf1, a key regulator of the nonsense-mediated decay pathway, and ATR, a key regulator of the DNA damage checkpoint pathway activated during replication stress.

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