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10.02.20 Jackson lab show that chronic irradiation induces histone loss in human cells

last modified Feb 10, 2020 10:19 AM
The Jackson lab, in collaboration with Public Health England, have shown that histones are lost in human cells when DNA damage is continually inflicted by exposure to low levels of chronic radiation. They show that this has effects on chromatin and cellular responses that could lead to age-related diseases.

Chronic irradiation of human cells reduces histone levels and deregulates gene expression

Lowe DJ et al. (2020) Scientific Reports 10, 2200.

DOI: 10.1038/s41598-020-59163-4.

 

Abstract from the paper

Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation.

We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6-20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence.

We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes.

Lowe hypothesis summary

The diagram summarises the hypothesis in this paper.

Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology.

 

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Read more about research in the Jackson lab.

Watch Steve Jackson describe his research on YouTube.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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