First Author | Yeo AJ | Year | 2014 |
Journal | PLoS One | Volume | 9 |
Issue | 3 | Pages | e90219 |
PubMed ID | 24637776 | Mgi Jnum | J:215106 |
Mgi Id | MGI:5604667 | Doi | 10.1371/journal.pone.0090219 |
Citation | Yeo AJ, 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 |
abstractText | 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. |