Proteomics

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H3K4me2 regulates the recovery of protein biosynthesis and homeostasis from UV-induced DNA damage during development and aging


ABSTRACT: DNA damage causes cancer, impairs development and accelerates aging. UV irradiation induces transcription-blocking lesions and defects in transcription-coupled nucleotide excision repair lead to developmental failure and premature aging in humans. Following DNA repair, the homeostatic processes need to be reestablished to ensure development and maintain tissue functionality. Here, we report that in C. elegans removal of the MLL/COMPASS H3K4 methyltransferase exacerbates the developmental growth retardation and accelerates aging, while depletion of the H3K4 demethylase, SPR-5, promotes developmental growth and extends lifespan amid UV-induced damage. We demonstrate that specifically the DDR-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 is essential for survival of UV-induced DNA damage. Our study uncovers a role of H3K4me2 in coordinating the recovery of protein biosynthesis and homeostasis that is required for developmental growth and longevity after DNA damage.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

SUBMITTER: David Meyer  

LAB HEAD: Univ.-Prof. Dr. Björn Schumacher

PROVIDER: PXD015354 | Pride | 2020-10-13

REPOSITORIES: Pride

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Publications

H3K4me2 regulates the recovery of protein biosynthesis and homeostasis following DNA damage.

Wang Siyao S   Meyer David H DH   Schumacher Björn B  

Nature structural & molecular biology 20201012 12


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, in Caenorhabditis elegans, removal of the WRAD complex of the MLL/COMPASS H3K4 methyltransferase exacerbates developmental growth retardation and acce  ...[more]

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