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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 Ca...

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Autores principales: Bujarrabal-Dueso, Arturo, Sendtner, Georg, Meyer, David H., Chatzinikolaou, Georgia, Stratigi, Kalliopi, Garinis, George A., Schumacher, Björn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113156/
https://www.ncbi.nlm.nih.gov/pubmed/36959262
http://dx.doi.org/10.1038/s41594-023-00942-8
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author Bujarrabal-Dueso, Arturo
Sendtner, Georg
Meyer, David H.
Chatzinikolaou, Georgia
Stratigi, Kalliopi
Garinis, George A.
Schumacher, Björn
author_facet Bujarrabal-Dueso, Arturo
Sendtner, Georg
Meyer, David H.
Chatzinikolaou, Georgia
Stratigi, Kalliopi
Garinis, George A.
Schumacher, Björn
author_sort Bujarrabal-Dueso, Arturo
collection PubMed
description 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.
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spelling pubmed-101131562023-04-20 The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities Bujarrabal-Dueso, Arturo Sendtner, Georg Meyer, David H. Chatzinikolaou, Georgia Stratigi, Kalliopi Garinis, George A. Schumacher, Björn Nat Struct Mol Biol Article 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. Nature Publishing Group US 2023-03-23 2023 /pmc/articles/PMC10113156/ /pubmed/36959262 http://dx.doi.org/10.1038/s41594-023-00942-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bujarrabal-Dueso, Arturo
Sendtner, Georg
Meyer, David H.
Chatzinikolaou, Georgia
Stratigi, Kalliopi
Garinis, George A.
Schumacher, Björn
The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities
title The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities
title_full The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities
title_fullStr The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities
title_full_unstemmed The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities
title_short The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities
title_sort dream complex functions as conserved master regulator of somatic dna-repair capacities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113156/
https://www.ncbi.nlm.nih.gov/pubmed/36959262
http://dx.doi.org/10.1038/s41594-023-00942-8
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