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

• Published in: Nature structural & molecular biology Vol. 30; no. 4; pp. 475 - 488
• Main Authors: Bujarrabal-Dueso, Arturo, Sendtner, Georg, Meyer, David H., Chatzinikolaou, Georgia, Stratigi, Kalliopi, Garinis, George A., Schumacher, Björn
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-04-2023; Nature Publishing Group
• Subjects: 13/1; 13/2; 13/31; 14/1; 38/91; 631/136/7; 631/208/211; 631/337/1427/1430; 631/337/1427/2566; 631/80/103; 64/11; 64/60; Aging; Animals; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Damage prevention; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA Damage; DNA Repair; ERCC1 protein; Gene expression; Germ cells; Germ Cells - metabolism; Humans; Life Sciences; Membrane Biology; Mice; Nematodes; Protein Structure; Somatic cells
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/s41594-023-00942-8

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.