Oxidative stress induces persistent telomeric DNA damage responsible for nuclear morphology change in Mammalian cells.

Published on Oct 29, 2014in PLOS ONE2.78
· DOI :10.1371/journal.pone.0110963
Elisa Coluzzi4
Estimated H-index: 4
Monica Colamartino3
Estimated H-index: 3
+ 4 AuthorsAntonella Sgura17
Estimated H-index: 17
One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG) and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5) in vitro with hydrogen peroxide (100 and 200 µM) for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei) and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs), we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect.
  • References (55)
  • Citations (49)
#1Nathan O'Callaghan (CSIRO: Commonwealth Scientific and Industrial Research Organisation)H-Index: 10
#2Natalie Baack (CSIRO: Commonwealth Scientific and Industrial Research Organisation)H-Index: 1
Last.Michael Fenech (CSIRO: Commonwealth Scientific and Industrial Research Organisation)H-Index: 56
view all 4 authors...
#1David B. Rhee (NIH: National Institutes of Health)H-Index: 3
#2Avik K. Ghosh (NIH: National Institutes of Health)H-Index: 9
Last.Yie Liu (NIH: National Institutes of Health)H-Index: 20
view all 5 authors...
#1Michael Fenech (CSIRO: Commonwealth Scientific and Industrial Research Organisation)H-Index: 56
#2Micheline Kirsch-Volders (Vrije Universiteit Brussel)H-Index: 59
Last.Philip Thomas (CSIRO: Commonwealth Scientific and Industrial Research Organisation)H-Index: 26
view all 10 authors...
#1Judit Pampalona (Autonomous University of Barcelona)H-Index: 6
#2David Soler (Autonomous University of Barcelona)H-Index: 7
Last.Laura Tusell (Autonomous University of Barcelona)H-Index: 16
view all 4 authors...
#1Aloysius Poh Leong Ting (NUS: National University of Singapore)H-Index: 3
#2Grace Kah Mun Low (NUS: National University of Singapore)H-Index: 6
Last.Manoor Prakash Hande (NUS: National University of Singapore)H-Index: 39
view all 4 authors...
Cited By49
#1José Manuel Orozco-Hernández (UAEM: Universidad Autónoma del Estado de México)
#2Leobardo Manuel Gómez Oliván (UAEM: Universidad Autónoma del Estado de México)H-Index: 1
Last.Octavio Dublán-García (UAEM: Universidad Autónoma del Estado de México)H-Index: 6
view all 9 authors...
View next paperOxidative stress shortens telomeres