2. Academic Validation
  3. Engineered chromatin readers track damaged chromatin dynamics in live cells and animals

Engineered chromatin readers track damaged chromatin dynamics in live cells and animals

  • Nat Commun. 2025 Nov 20;16(1):10127. doi: 10.1038/s41467-025-65706-y.
Richard Cardoso da Silva 1,  Kristeli Eleftheriou 2,  Davide C Recchia 2,  Vincent Portegijs 3,  Douwe Ten Bulte 2,  Niklas Kupfer 2,  Nathalie P Vroegindeweij-de Wagenaar 2,  Xabier Vergara 4 5,  Ayoub Ouchene 4 5,  Sander van den Heuvel 3,  Tuncay Baubec 6
Affiliations

Affiliations

  • 1 Genome Biology and Epigenetics, Institute of Biodynamics and Biocomplexity, Department of Biology, Utrecht University, Utrecht, The Netherlands. [email protected].
  • 2 Genome Biology and Epigenetics, Institute of Biodynamics and Biocomplexity, Department of Biology, Utrecht University, Utrecht, The Netherlands.
  • 3 Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Utrecht University, Utrecht, The Netherlands.
  • 4 Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • 5 Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • 6 Genome Biology and Epigenetics, Institute of Biodynamics and Biocomplexity, Department of Biology, Utrecht University, Utrecht, The Netherlands. [email protected].
PMID: 41266351 DOI: 10.1038/s41467-025-65706-y
Abstract

DNA damage is a constant threat to genome integrity and function. Diminished capacity for DNA repair is linked to many human diseases, therefore, understanding the molecular pathways responding to DNA damage is key for developing novel therapies. Lack of unbiased probes to report DNA damage dynamics in living cells and Animals limits our current efforts to completely understand DNA repair processes. In this study, we overcome these limitations by engineering protein probes containing the tandem-BRCT domain of MCPH1, which we show to have a specific affinity for the DNA-damage-associated histone MARK γH2AX. We employ these probes to track DNA damage dynamics in living cells exposed to a panel of different genotoxic insults, to visualize DNA damage targeted to heterochromatinised satellite repeats, and to map DNA double strand breaks genome-wide. Finally, we highlight the versatility of our probe to visualize programmed double strand breaks during gametogenesis in C. elegans. Taken together, we present a novel protein probe with broad application potential for DNA damage research.

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