In the Journal Club this month we will exploring a new study published in Nature Structural and Molecular Biology, where researchers demonstrated that by manipulating the DREAM protein complex, a major regulator of DNA damage response, it may be possible to reduce the number of DNA mutations accumulated with age. Dr. Oliver Medvedik will be hosting the Journal Club which will be streamed live to the Lifespan.io Facebook page at 12:00 Eastern time on April 25th.
You may wish to read our news story ‘Inhibiting DREAM for Enhanced DNA Damage Repair’ on this study as a primer for reading the published paper.
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.
Literature
Bujarrabal-Dueso, A., Sendtner, G., Meyer, D. H., Chatzinikolaou, G., Stratigi, K., Garinis, G. A., & Schumacher, B. (2023). The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities. Nature Structural & Molecular Biology, 1-14.
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