Nucleic Acids Research Advance Access originally published online on May 18, 2009
Nucleic Acids Research 2009 37(13):4315-4321; doi:10.1093/nar/gkp385
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Nucleic Acids Research, 2009, Vol. 37, No. 13 4315-4321
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gene Regulation, Chromatin and Epigenetics |
R-loops do not accumulate in transcription-defective hpr1-101 mutants: implications for the functional role of THO/TREX
Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Av. Américo Vespucio s/n, 41092 SEVILLA, Spain
*To whom correspondence should be addressed. Tel: +34 954 468 372; Fax: +34 954 461 664; Email: aguilo{at}us.es
Received March 23, 2009. Revised April 27, 2009. Accepted April 28, 2009.
To get further insight into the effect that THO/TREX and R-loops have in transcription-associated recombination and transcription, we analyzed the ability to form R-loops of hpr1-101, a THO mutation that impairs transcription and mRNP biogenesis without triggering hyper-recombination. Human AID, a cytidine deaminase that acts on ssDNA displaced by RNA-DNA hybrids, strongly induced both hyper-recombination and hyper-mutation in hpr1-101, similar to hpr1
mutants. However, in contrast to hpr1
, AID-induced mutations in hpr1-101 occur at similar frequencies in both the transcribed and non-transcribed strands, implying that the enhanced AID action in these mutants is not caused by co-transcriptional R-loops. These results indicate for the first time that THO has a transcriptional function that is not mediated by R-loops, providing a new perspective for the understanding of the coupling of transcription with mRNP biogenesis and export.