P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance

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作者：
Raphael Loll-Krippleber
Grant W. Brown
机构：
[1] University of Toronto,Department of Biochemistry and Donnelly Centre
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Nature Communications | / 8卷
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摘要：
mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and leads to toxic acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response.
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  • [1] Zeman MK(2014)Causes and consequences of replication stress Nat. Cell. Biol. 16 2-9
  • [2] Cimprich KA(2011)Prevention of DNA re-replication in eukaryotic cells J. Mol. Cell Biol. 3 13-22
  • [3] Truong LN(2009)The S-phase checkpoint: targeting the replication fork Biol. Cell 101 617-627
  • [4] Wu X(2002)A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage Proc. Natl Acad. Sci. USA 99 16934-16939
  • [5] Segurado M(2001)Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p Mol. Biol. Cell. 12 2987-3003
  • [6] Tercero JA(2006)Role of the iron mobilization and oxidative stress regulons in the genomic response of yeast to hydroxyurea Mol. Genet. Genomic 275 114-124
  • [7] Chang M(2013)Checkpoint kinases regulate a global network of transcription factors in response to DNA damage Cell Rep. 4 174-188
  • [8] Bellaoui M(2012)Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress Nat. Cell. Biol. 14 966-976
  • [9] Boone C(2015)Yeast proteome dynamics from single cell imaging and automated analysis Cell 161 1413-1424
  • [10] Brown GW(2007)Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases Proc. Natl Acad. Sci. USA 104 10364-10369
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