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DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin

Jakob, Burkhard ; Splinter, Jörn ; Conrad, Sandro ; Voss, Kay-Obbe ; Zink, Daniele ; Durante, Marco ; Löbrich, Markus ; Taucher-Scholz, Gisela (2022):
DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin. (Publisher's Version)
In: Nucleic Acids Research, 39 (15), pp. 6489-6499. Oxford University Press, ISSN 0305-1048, e-ISSN 1362-4962,
DOI: 10.26083/tuprints-00019032,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin
Language: English
Abstract:

DNA double-strand breaks (DSBs) can induce chromosomal aberrations and carcinogenesis and their correct repair is crucial for genetic stability. The cellular response to DSBs depends on damage signaling including the phosphorylation of the histone H2AX (γH2AX). However, a lack of γH2AX formation in heterochromatin (HC) is generally observed after DNA damage induction. Here, we examine γH2AX and repair protein foci along linear ion tracks traversing heterochromatic regions in human or murine cells and find the DSBs and damage signal streaks bending around highly compacted DNA. Given the linear particle path, such bending indicates a relocation of damage from the initial induction site to the periphery of HC. Real-time imaging of the repair protein GFP-XRCC1 confirms fast recruitment to heterochromatic lesions inside murine chromocenters. Using single-ion microirradiation to induce localized DSBs directly within chromocenters, we demonstrate that H2AX is early phosphorylated within HC, but the damage site is subsequently expelled from the center to the periphery of chromocenters within ∼20 min. While this process can occur in the absence of ATM kinase, the repair of DSBs bordering HC requires the protein. Finally, we describe a local decondensation of HC at the sites of ion hits, potentially allowing for DSB movement via physical forces.

Journal or Publication Title: Nucleic Acids Research
Volume of the journal: 39
Issue Number: 15
Publisher: Oxford University Press
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 23 Mar 2022 12:40
Last Modified: 23 Mar 2022 12:41
DOI: 10.26083/tuprints-00019032
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-190321
Additional Information:

Supplementary Data: https://t1p.de/qvc7f

URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/19032
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