Research Paper Volume 4, Issue 11 pp 823—842
Depletion of nuclear histone H2A variants is associated with chronic DNA damage signaling upon drug-evoked senescence of human somatic cells
- 1 BRIMS, Thermo Fisher Scientific, Cambridge, MA
- 2 Buck Institute for Research on Aging, Novato, CA
- 3 Georgia Institute of Technology, Atlanta, GA
- 4 University de Libra, Center of Excellency Regenerar, Cali, Colombia
Received: November 26, 2012 Accepted: November 30, 2012 Published: December 6, 2012
https://doi.org/10.18632/aging.100507How to Cite
Copyright: © 2022 Lopez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cellular senescence is associated with global chromatin changes, altered gene expression, and activation of chronic DNA damage signaling. These events ultimately lead to morphological and physiological transformations in primary cells. In this study, we show that chronic DNA damage signals caused by genotoxic stress impact the expression of histones H2A family members and lead to their depletion in the nuclei of senescent human fibroblasts. Our data reinforce the hypothesis that progressive chromatin destabilization may lead to the loss of epigenetic information and impaired cellular function associated with chronic DNA damage upon drug-evoked senescence. We propose that changes in the histone biosynthesis and chromatin assembly may directly contribute to cellular aging. In addition, we also outline the method that allows for quantitative and unbiased measurement of these changes.