Susan Gasser - Chromatin and Nucleosome Density: How DNA Damage Response Alters Chromatin Dynamics

The Monthly Seminar on Physical Genomics - March 31, 2023
Hosted by the Center for Physical Genomics and Engineering at Northwestern University
In eukaryotes, nucleosomes are essential for maintenance of genome integrity and proper chromatin organization. Histones, however, are often evicted at the site of DNA breaks, which facilitates resection and the recruitment of repair factors at the break. Recent findings from the Gasser group showed that total nuclear levels of core histones also drop in response to DNA damage checkpoint response. The drop stems from the degradation of histones and depends on the chromatin remodeler complex INO80 and the proteasome. Chromatin decompaction and increased fiber flexibility accompany histone degradation. Quantitative mass spectrometry of the chromatin-associated proteome confirms a major depletion of RNA polymerases and most nucleosome remodelers in response to the DNA damage checkpoint, along with a 20-40% loss of core histones. Ubiquitin ligases are among the proteins that show an increase in association with chromatin, and in some cases, this requires the INO80 remodeler. Both the remodeler and histone ubiquitination contribute to the rate of homology search during repair by homologous recombination, confirming a physiological role for histone degradation in the mechanics of DNA repair.

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