R-Loops in Proliferating Cells but Not in the Brain: Implications for AOA2 and Other Autosomal Recessive Ataxias

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R-Loops in Proliferating Cells but Not in the Brain: Implications for AOA2 and Other Autosomal Recessive Ataxias
Title:
R-Loops in Proliferating Cells but Not in the Brain: Implications for AOA2 and Other Autosomal Recessive Ataxias
Journal Title:
PLoS One
Keywords:
Publication Date:
17 March 2014
Citation:
Yeo AJ, Becherel OJ, Luff JE, Cullen JK, Wongsurawat T, 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. doi:10.1371/journal.pone.0090219
Abstract:
Disruption 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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This work was supported by the Australian Research Council (ARC) and the BrAshA-T Foundation to MFL. AJY is a recipient of the International Postgraduate Research Scholarship (IPRS) awarded by the Department of Innovation, Australian Government, and the UQCentennial and UQAdvantage scholarships awarded by the University of Queensland, Australia.
Description:
ISSN:
1932-6203
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