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DNA repair

Histones have got to go

Nature Reviews Molecular Cell Biology volume 18, page 139 (2017)Cite this article

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Chromatin properties are greatly modulated by the nucleosome occupancy levels. Using a radiometric mass spectrometry approach in budding yeast, the authors noted that protein levels of core histones (but not of histone variants) decrease considerably following the induction of DSBs by the chemical compound zeocin or by ionizing radiation. Genome-wide nucleosome mapping revealed that this was associated with widespread reduction of nucleosome occupancy in chromatin, which occurred rapidly — within 30 minutes — after the induction of DSBs. Inhibition of the proteasome complex suppressed these effects, collectively indicating that DNA damage induces the degradation of core histones, leading to a genome-wide decrease in nucleosome occupancy.

High-speed, super-resolution imaging of yeast cells with fluorescently labelled chromatin domains revealed the volumetric expansion of these domains following zeocin treatment, showing that DNA damage promotes chromatin decompaction. Furthermore, zeocin enhanced the mobility of chromatin domains as well as increased the average distances between individual domains, demonstrating that DNA damage is associated with increased chromatin fibre flexibility and, confirming previous results, with increased chromosome mobility. Reducing core histone expression could induce chromatin decompaction and chromosome mobility even in the absence of DNA damage, suggesting that decreased histone levels are directly linked to increased chromatin dynamicity.

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References

  1. Hauer, M. H. et al. Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates. Nat. Struct. Mol. Biol. http://dx.doi.org/10.1038/nsmb.3347 (2017)

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  1. Paulina Strzyz
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Strzyz, P. Histones have got to go. Nat Rev Mol Cell Biol 18, 139 (2017). https://doi.org/10.1038/nrm.2017.2

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