Histone H1 eviction by the histone chaperone SET reduces cell survival following DNA damage.

Autor:	Mandemaker IK; Erasmus MC, University Medical Center Rotterdam, Department of Molecular Genetics, Oncode Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands., Zhou D; Erasmus MC, University Medical Center Rotterdam, Department of Molecular Genetics, Oncode Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands., Bruens ST; Erasmus MC, University Medical Center Rotterdam, Department of Molecular Genetics, Oncode Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands., Dekkers DH; Proteomics Center, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands., Verschure PJ; Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands., Edupuganti RR; The Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus, 91904 Jerusalem, Israel., Meshorer E; The Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus, 91904 Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel., Demmers JAA; Proteomics Center, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands., Marteijn JA; Erasmus MC, University Medical Center Rotterdam, Department of Molecular Genetics, Oncode Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands J.Marteijn@erasmusmc.nl.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2020 May 11; Vol. 133 (9). Date of Electronic Publication: 2020 May 11.
DOI:	10.1242/jcs.235473
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu