Real-Time Tracking of Parental Histones Reveals Their Contribution to Chromatin Integrity Following DNA Damage

• Published in: Molecular cell Vol. 64; no. 1; pp. 65 - 78
• Main Authors: Adam, Salomé, Dabin, Juliette, Chevallier, Odile, Leroy, Olivier, Baldeyron, Céline, Corpet, Armelle, Lomonte, Patrick, Renaud, Olivier, Almouzni, Geneviève, Polo, Sophie E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.10.2016; Cell Press
• Subjects: Biochemistry, Molecular Biology; Cell Line, Tumor; Chromatin - chemistry; Chromatin - metabolism; Chromatin - radiation effects; Chromatin Assembly and Disassembly; DNA Damage; DNA Repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fluorescent Antibody Technique - methods; Genomic Instability; Genomics; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Histones - antagonists & inhibitors; Histones - genetics; Histones - metabolism; Humans; Life Sciences; Osteoblasts - cytology; Osteoblasts - metabolism; Osteoblasts - radiation effects; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Ultraviolet Rays
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2016.08.019

Chromatin integrity is critical for cell function and identity but is challenged by DNA damage. To understand how chromatin architecture and the information that it conveys are preserved or altered following genotoxic stress, we established a system for real-time tracking of parental histones, which characterize the pre-damage chromatin state. Focusing on histone H3 dynamics after local UVC irradiation in human cells, we demonstrate that parental histones rapidly redistribute around damaged regions by a dual mechanism combining chromatin opening and histone mobilization on chromatin. Importantly, parental histones almost entirely recover and mix with new histones in repairing chromatin. Our data further define a close coordination of parental histone dynamics with DNA repair progression through the damage sensor DDB2 (DNA damage-binding protein 2). We speculate that this mechanism may contribute to maintaining a memory of the original chromatin landscape and may help preserve epigenome stability in response to DNA damage. [Display omitted] •Parental H3 histones redistribute to the periphery of UVC-damaged regions•The redistribution involves histone mobilization on chromatin and chromatin opening•Parental histones recover massively during repair progression•Parental histone dynamics may help coordinate DNA repair with epigenome integrity Adam et al. identify a conservative process coordinated with UVC damage repair progression, whereby parental histones rapidly redistribute away from damaged chromatin regions and subsequently recover. Parental histone dynamics coupled to DNA repair may contribute to maintaining epigenome integrity upon DNA damage.