Chromatin adaptors and TOPBP1 condensates cooperate to organize ATM signaling
Abstract
DNA damage response proteins frequently accumulate in biomolecular condensates, yet how these structures cooperate with classical adaptor-mediated recruitment mechanisms to organize DNA damage signaling remains poorly understood. Here, we identify Treacle and the ATM adaptor NBS1 as prominent components of TOPBP1 condensates and show that these structures activate ATM signaling in the absence of DNA damage. At rDNA breaks, Treacle recruits NBS1 and TOPBP1 through genetically separable interaction modules. Acute protein degradation further revealed that Treacle is required for condensate assembly, whereas TOPBP1 remains continuously required for condensate maintenance. Finally, we show that efficient ATM accumulation at IR-induced DNA double-strand breaks similarly depends on both NBS1 and TOPBP1, indicating that this two-component mechanism is not restricted to nucleolar DNA damage. Together, our findings support a two-component model in which adaptor proteins provide molecular specificity, whereas TOPBP1 condensates create the spatial organization required for robust ATM signaling.
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BibTeX
@misc{mooser2026chromatin,
title = {{Chromatin adaptors and TOPBP1 condensates cooperate to organize ATM signaling}},
author = {Clémence Mooser and Jihane Basbous and Nathalie Varisco and Tom Egger and Mònica Torres Esteban and Johannes Leyrer and Andrea Hänel and Vira Chea and Alain Jeanrenaud and Angelos Constantinou and Manuel Stucki},
howpublished = {HAL},
year = {2026},
month = aug,
doi = {10.64898/2026.08.21.746129},
url = {https://hal.science/hal-05742913v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Chromatin adaptors and TOPBP1 condensates cooperate to organize ATM signaling
AU - Clémence Mooser
AU - Jihane Basbous
AU - Nathalie Varisco
AU - Tom Egger
AU - Mònica Torres Esteban
AU - Johannes Leyrer
AU - Andrea Hänel
AU - Vira Chea
AU - Alain Jeanrenaud
AU - Angelos Constantinou
AU - Manuel Stucki
PY - 2026
DA - 2026/08/21
PB - HAL
DO - 10.64898/2026.08.21.746129
UR - https://hal.science/hal-05742913v1
AB - DNA damage response proteins frequently accumulate in biomolecular condensates, yet how these structures cooperate with classical adaptor-mediated recruitment mechanisms to organize DNA damage signaling remains poorly understood. Here, we identify Treacle and the ATM adaptor NBS1 as prominent components of TOPBP1 condensates and show that these structures activate ATM signaling in the absence of DNA damage. At rDNA breaks, Treacle recruits NBS1 and TOPBP1 through genetically separable interaction modules. Acute protein degradation further revealed that Treacle is required for condensate assembly, whereas TOPBP1 remains continuously required for condensate maintenance. Finally, we show that efficient ATM accumulation at IR-induced DNA double-strand breaks similarly depends on both NBS1 and TOPBP1, indicating that this two-component mechanism is not restricted to nucleolar DNA damage. Together, our findings support a two-component model in which adaptor proteins provide molecular specificity, whereas TOPBP1 condensates create the spatial organization required for robust ATM signaling.
ER -