Journal of Biosciences

, Volume 28, Issue 1, pp 57–60 | Cite as

H2O2-induced higher order chromatin degradation: A novel mechanism of oxidative genotoxicity



The genotoxicity of reactive oxygen species (ROS) is well established. The underlying mechanism involves oxidation of DNA by ROS. However, we have recently shown that hydrogen peroxide (H2O2), the major mediator of oxidative stress, can also cause genomic damage indirectly. Thus, H2O2 at pathologically relevant concentrations rapidly induces higher order chromatin degradation (HOCD), i.e. enzymatic excision of chromatin loops and their oligomers at matrix-attachment regions. The activation of endonuclease that catalyzes HOCD is a signalling event triggered specifically by H2O2. The activation is not mediated by an influx of calcium ions, but resting concentrations of intracellular calcium ions are required for the maintenance of the endonuclease in an active form. Although H2O2-induced HOCD can efficiently dismantle the genome leading to cell death, under sublethal oxidative stress conditions H2O2-induced HOCD may be the major source of somatic mutations.


Neoplasia neurodegeneration oxidative stress somatic mutations 

Abbreviations used


Higher order chromatin degradation


matrix attachment region


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Copyright information

© Indian Academy of Sciences 2003

Authors and Affiliations

  1. 1.Department of Neurobiology and AnatomyWest Virginia University School of MedicineMorgantownUSA

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