The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities

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. In this work, the authors show that the DREAM complex suppresses the expression of numerous DNA-repair proteins in somatic cells. Suppression of the DREAM complex, either by altering individual components in Caenorhabditis elegans or chemical inhibition in human cells and progeroid mice, results in increased resistance to various DNA-damage sources during development and aging.