dc.contributor.authorYeo, Abrey J.
dc.contributor.authorBecherel, Olivier J.
dc.contributor.authorLuff, John E.
dc.contributor.authorCullen, Jason K.
dc.contributor.authorWongsurawat, Thidathip
dc.contributor.authorJenjaroenpoon, Piroon
dc.contributor.authorKuznetsov, Vladimir A.
dc.contributor.authorMcKinnon, Peter J.
dc.contributor.authorLavin, Martin F.
dc.contributor.editorGueven, Nuri*
dc.identifier.citationYeo, A. J., Becherel, O. J., Luff, J. E., Cullen, J. K., Wongsurawat, T., Jenjaroenpoon, P., et al. (2014). R-Loops in Proliferating Cells but Not in the Brain: Implications for AOA2 and Other Autosomal Recessive Ataxias. PLoS ONE, 9(3), e90219-.en_US
dc.description.abstractDisruption of the Setx gene, defective in ataxia oculomotor apraxia type 2 (AOA2) leads to the accumulation of DNA/RNA hybrids (R-loops), failure of meiotic recombination and infertility in mice. We report here the presence of R-loops in the testes from other autosomal recessive ataxia mouse models, which correlate with fertility in these disorders. R-loops were coincident in cells showing high basal levels of DNA double strand breaks and in those cells undergoing apoptosis. Depletion of Setx led to high basal levels of R-loops and these were enhanced further by DNA damage both in vitro and in vivo in tissues with proliferating cells. There was no evidence for accumulation of R-loops in the brains of mice where Setx, Atm, Tdp1 or Aptx genes were disrupted. These data provide further evidence for genome destabilization as a consequence of disrupted transcription in the presence of DNA double strand breaks arising during DNA replication or recombination. They also suggest that R-loop accumulation does not contribute to the neurodegenerative phenotype in these autosomal recessive ataxias.en_US
dc.relation.ispartofseriesPLoS ONEen_US
dc.rights© 2014 Yeo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectDRNTU::Engineering::Computer science and engineering
dc.titleR-Loops in proliferating cells but not in the brain : implications for AOA2 and other autosomal recessive ataxiasen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Computer Engineeringen_US
dc.description.versionPublished versionen_US

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