The GATAD2B-NuRD complex drives DNA:RNA hybrid-dependent chromatin boundary formation upon DNA damage.

Autor:	Liu Z; Sir William Dunn School of Pathology, South Parks Road, Oxford, OX1 3RE, United Kingdom., Ajit K; Sir William Dunn School of Pathology, South Parks Road, Oxford, OX1 3RE, United Kingdom., Wu Y; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University International Cancer Center, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, 518055, Shenzhen, China., Zhu WG; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University International Cancer Center, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, 518055, Shenzhen, China., Gullerova M; Sir William Dunn School of Pathology, South Parks Road, Oxford, OX1 3RE, United Kingdom. monika.gullerova@path.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2024 Jun; Vol. 43 (12), pp. 2453-2485. Date of Electronic Publication: 2024 May 08.
DOI:	10.1038/s44318-024-00111-7
Abstrakt:	Double-strand breaks (DSBs) are the most lethal form of DNA damage. Transcriptional activity at DSBs, as well as transcriptional repression around DSBs, are both required for efficient DNA repair. The chromatin landscape defines and coordinates these two opposing events. However, how the open and condensed chromatin architecture is regulated remains unclear. Here, we show that the GATAD2B-NuRD complex associates with DSBs in a transcription- and DNA:RNA hybrid-dependent manner, to promote histone deacetylation and chromatin condensation. This activity establishes a spatio-temporal boundary between open and closed chromatin, which is necessary for the correct termination of DNA end resection. The lack of the GATAD2B-NuRD complex leads to chromatin hyperrelaxation and extended DNA end resection, resulting in homologous recombination (HR) repair failure. Our results suggest that the GATAD2B-NuRD complex is a key coordinator of the dynamic interplay between transcription and the chromatin landscape, underscoring its biological significance in the RNA-dependent DNA damage response. (© 2024. The Author(s).)
Databáze:	MEDLINE
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