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Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles

  作者 Gomez-Gonzalez, B; Garcia-Rubio, M; Bermejo, R; Gaillard, H; Shirahige, K; Marin, A; Foiani, M; Aguilera, A  
  选自 期刊  EMBO journal;  卷期  2011年30-15;  页码  3106-3119  
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[摘要]THO/TREX is a conserved nuclear complex that functions in mRNP biogenesis and prevents transcription-associated recombination. Whether or not it has a ubiquitous role in the genome is unknown. Chromatin immunoprecipitation (ChIP)-chip studies reveal that the Hpr1 component of THO and the Sub2 RNA-dependent ATPase have genome-wide distributions at active ORFs in yeast. In contrast to RNA polymerase II, evenly distributed from promoter to termination regions, THO and Sub2 are absent at promoters and distributed in a gradual 5' -> 3' gradient. This is accompanied by a genome-wide impact of THO-Sub2 deletions on expression of highly expressed, long and high G + C-content genes. Importantly, ChIP-chips reveal an over-recruitment of Rrm3 in active genes in THO mutants that is reduced by RNaseH1 overexpression. Our work establishes a genome-wide function for THO-Sub2 in transcription elongation and mRNP biogenesis that function to prevent the accumulation of transcription-mediated replication obstacles, including R-loops. The EMBO Journal (2011) 30, 3106-3119. doi:10.1038/emboj.2011.206; Published online 24 June 2011

 
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