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Unfolding the story of chromatin organization in senescent cells

Swanson, Eric C.
Rapkin, Lindsy M.
Bazett-Jones, David P.
Lawrence, Jeanne B.
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Abstract

Cell senescence, the permanent withdrawal of a cell from the cell cycle, is characterized by dramatic, cytological scale changes to DNA condensation throughout the genome. While prior emphasis has been placed on increases in heterochromatin, such as the formation of compact Senescent Associated Heterochromatin Foci (SAHF) structures, our recent findings showed that SAHF formation is preceded by the unravelling of constitutive heterochromatin into visibly extended structures, which we have termed Senescent Associated Distension of Satellites or SADS. Interestingly, neither of these marked changes in DNA condensation appear to be mediated by changes in canonical, heterochromatin-associated histone modifications. Rather, several observations suggest that these events may be facilitated by changes in LaminB1 levels and/or other factors that control higher-order chromatin architecture. Here, we review what is known about senescence-associated chromatin reorganization and present preliminary results using high-resolution microscopy techniques to show that each peri/centromeric satellite in senescent cells is comprised of several condensed domains connected by thin fibrils of satellite DNA. We then discuss the potential importance of these striking changes in chromatin condensation for cell senescence, and also as a model to provide a needed window into the higher-order packaging of the genome.

Source

Nucleus. 2015 Jul 4;6(4):254-60. doi: 10.1080/19491034.2015.1057670. Link to article on publisher's site.

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DOI
10.1080/19491034.2015.1057670
PubMed ID
26107557
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Notes

First author Eric Swanson is a doctoral student in the Cell Biology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

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