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

Imke K. Mandemaker, Di Zhou, Serena T. Bruens, Dick H. Dekkers, Pernette J. Verschure, Raghu R. Edupuganti, Eran Meshorer, Jeroen A.A. Demmers, Jurgen A. Marteijn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageAmerican English
Article numberjcs235473
JournalJournal of Cell Science
Volume133
Issue number9
DOIs
StatePublished - May 2020

Bibliographical note

Publisher Copyright:
© 2020. Published by The Company of Biologists Ltd.

Keywords

  • DNA damage
  • Histone H1
  • Histone chaperone
  • SET

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