Histone H1 eviction by the histone chaperone SET reduces cell survival following DNA damage
| Autor: | Jeroen Demmers, Jurgen A. Marteijn, Eran Meshorer, Serena T. Bruens, Pernette J. Verschure, Di Zhou, Raghu Ram Edupuganti, Imke K Mandemaker, Dick H. W. Dekkers |
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| Přispěvatelé: | Synthetic Systems Biology (SILS, FNWI), Molecular Genetics, Biochemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
biology DNA repair DNA damage Cell Survival Cell Biology Genotoxic Stress Chromatin remodeling Chromatin Cell biology Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Histone Histone H1 chemistry 030220 oncology & carcinogenesis biology.protein Histone Chaperones DNA 030304 developmental biology DNA Damage |
| Zdroj: | Journal of Cell Science, 133:jcs235473. Company of Biologists Ltd Journal of Cell Science, 133(9):jcs235473. Company of Biologists Ltd |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Many chromatin remodeling and modifying proteins are involved in the DNA damage response, where they stimulate repair or induce DNA damage signaling. Interestingly, we identified that downregulation of the histone H1 (H1)-interacting protein SET results in increased resistance to a wide variety of DNA damaging agents. We found that this increased resistance does not result from alleviation of an inhibitory effect of SET on DNA repair but, rather, is the consequence of a suppressed apoptotic response to DNA damage. Furthermore, we provide evidence that the histone chaperone SET is responsible for the eviction of H1 from chromatin. Knockdown of H1 in SET-depleted cells resulted in re-sensitization of cells to DNA damage, suggesting that the increased DNA damage resistance in SET-depleted cells is the result of enhanced retention of H1 on chromatin. Finally, clonogenic survival assays showed that SET and p53 act epistatically in the attenuation of DNA damage-induced cell death. Taken together, our data indicate a role for SET in the DNA damage response as a regulator of cell survival following genotoxic stress.This article has an associated First Person interview with the first author of the paper. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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