RRC ID 76129
Author Bujarrabal-Dueso A, Sendtner G, Meyer DH, Chatzinikolaou G, Stratigi K, Garinis GA, Schumacher B.
Title The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities.
Journal Nat Struct Mol Biol
Abstract The DNA-repair capacity in somatic cells is limited compared with that in germ cells. It has remained unknown whether not only lesion-type-specific, but overall repair capacities could be improved. Here we show that the DREAM repressor complex curbs the DNA-repair capacities in somatic tissues of Caenorhabditis elegans. Mutations in the DREAM complex induce germline-like expression patterns of multiple mechanisms of DNA repair in the soma. Consequently, DREAM mutants confer resistance to a wide range of DNA-damage types during development and aging. Similarly, inhibition of the DREAM complex in human cells boosts DNA-repair gene expression and resistance to distinct DNA-damage types. DREAM inhibition leads to decreased DNA damage and prevents photoreceptor loss in progeroid Ercc1-/- mice. We show that the DREAM complex transcriptionally represses essentially all DNA-repair systems and thus operates as a highly conserved master regulator of the somatic limitation of DNA-repair capacities.
Volume 30(4)
Pages 475-488
Published 2023-4-1
DOI 10.1038/s41594-023-00942-8
PII 10.1038/s41594-023-00942-8
PMID 36959262
PMC PMC10113156
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism DNA / metabolism DNA Damage DNA Repair Germ Cells / metabolism Humans Mice
Resource
C.elegans tm3886 tm1489 tm4539 tm1524 tm1145