Universität zu Köln

Wang, Siyao, Meyer, David H. and Schumacher, Bjoern (2020). H3K4me2 regulates the recovery of protein biosynthesis and homeostasis following DNA damage. Nat. Struct. Mol. Biol., 27 (12). S. 1165 - 1183. BERLIN: NATURE RESEARCH. ISSN 1545-9985

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Abstract

DNA damage causes cancer, impairs development and accelerates aging. Transcription-blocking lesions and transcription-coupled repair defects lead to developmental failure and premature aging in humans. Following DNA repair, homeostatic processes need to be reestablished to ensure development and maintain tissue functionality. Here, we report that, inCaenorhabditis elegans, removal of the WRAD complex of the MLL/COMPASS H3K4 methyltransferase exacerbates developmental growth retardation and accelerates aging, while depletion of the H3K4 demethylases SPR-5 and AMX-1 promotes developmental growth and extends lifespan amid ultraviolet-induced damage. We demonstrate that DNA-damage-induced H3K4me2 is associated with the activation of genes regulating RNA transport, splicing, ribosome biogenesis and protein homeostasis and regulates the recovery of protein biosynthesis that ensures survival following genotoxic stress. Our study uncovers a role for H3K4me2 in coordinating the recovery of protein biosynthesis and homeostasis required for developmental growth and longevity after DNA damage. A directed genetic screen of chromatin regulators reveals that histone H3K4me2 deposition facilitates recovery of protein biosynthesis following UV-induced DNA damage repair and extends lifespan inC. elegans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wang, Siyao UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, David H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-315217
DOI:	10.1038/s41594-020-00513-1
Journal or Publication Title:	Nat. Struct. Mol. Biol.
Volume:	27
Number:	12
Page Range:	S. 1165 - 1183
Date:	2020
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	1545-9985
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEOTIDE EXCISION-REPAIR; LIFE-SPAN; HISTONE MODIFICATIONS; DEPENDENT MANNER; AMINO-ACIDS; CHROMATIN; TRANSCRIPTION; METHYLATION; DEMETHYLASE; CELLS Multiple languages Biochemistry & Molecular Biology; Biophysics; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31521