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

Arturo Bujarrabal-Dueso1,2, Georg Sendtner1,2, David H Meyer1,2

  • 1Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.

Nature Structural & Molecular Biology
|March 24, 2023
PubMed

Insights

The DREAM complex limits DNA repair in somatic cells. Inhibiting this complex enhances DNA repair, offering protection against various DNA damage types and aging.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Somatic cells exhibit limited DNA repair capacity compared to germ cells.
  • The overall DNA repair capacity and its regulation in somatic cells remain poorly understood.

Purpose of the Study:

  • To investigate whether overall DNA repair capacities in somatic cells can be enhanced.
  • To identify regulatory mechanisms controlling somatic DNA repair limitations.

Main Methods:

  • Utilized Caenorhabditis elegans models with mutations in the DREAM repressor complex.
  • Examined DNA repair gene expression patterns in somatic cells.
  • Assessed DNA damage resistance in DREAM mutants and human cells with DREAM inhibition.
  • Investigated the effects of DREAM inhibition in progeroid Ercc1-/- mice.

Main Results:

  • Mutations in the DREAM complex led to germline-like DNA repair gene expression in somatic cells.
  • DREAM mutants showed increased resistance to diverse DNA-damaging agents during development and aging.
  • DREAM complex inhibition boosted DNA repair gene expression and resistance to DNA damage in human cells.
  • DREAM inhibition reduced DNA damage and prevented photoreceptor loss in Ercc1-/- mice.

Conclusions:

  • The DREAM repressor complex acts as a master regulator, transcriptionally repressing most DNA repair systems in somatic cells.
  • Inhibiting the DREAM complex enhances DNA repair capacity, offering a potential therapeutic strategy against DNA damage and aging-related diseases.

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