Nature Structural & Molecular Biology
12, 794 - 800 (2005)
Published online: 7 August 2005; | doi:10.1038/nsmb972
Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1Handan Kaygun1, 2
& William F Marzluff1, 2, 31
Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 2
Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 3
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Correspondence should be addressed to William F Marzluff marzluff@med.unc.edu 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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