Title |
R-Loops in Proliferating Cells but Not in the Brain: Implications for AOA2 and Other Autosomal Recessive Ataxias
|
---|---|
Published in |
PLOS ONE, March 2014
|
DOI | 10.1371/journal.pone.0090219 |
Pubmed ID | |
Authors |
Abrey J. Yeo, Olivier J. Becherel, John E. Luff, Jason K. Cullen, Thidathip Wongsurawat, Piroon Jenjaroenpoon, Vladimir A. Kuznetsov, Peter J. McKinnon, Martin F. Lavin |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 3% |
Israel | 1 | 1% |
Unknown | 76 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 19 | 24% |
Student > Ph. D. Student | 14 | 18% |
Student > Master | 8 | 10% |
Student > Bachelor | 7 | 9% |
Professor | 5 | 6% |
Other | 10 | 13% |
Unknown | 16 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 28 | 35% |
Agricultural and Biological Sciences | 19 | 24% |
Medicine and Dentistry | 9 | 11% |
Arts and Humanities | 2 | 3% |
Neuroscience | 2 | 3% |
Other | 3 | 4% |
Unknown | 16 | 20% |