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Title: Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

Abstract

DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown thatmore » persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
Life Sciences Division
OSTI Identifier:
982831
Report Number(s):
LBNL-3098E
Journal ID: ISSN 0027-5107; MUREAV; TRN: US201014%%82
DOE Contract Number:  
DE-AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Mutation Research
Additional Journal Information:
Related Information: Journal Publication Date: January 2010; Journal ID: ISSN 0027-5107
Country of Publication:
United States
Language:
English
Subject:
59; ARCHITECTURE; CHROMATIN; DNA; DNA DAMAGES; DOORS; HISTONES; IONIZING RADIATIONS; KINETICS; MACHINERY; MITOSIS; MODIFICATIONS; PROGENY; PROTEINS; RADIATION QUALITY; REPAIR; RESOLUTION; DSB, H2AX, ATMp, 53BP1, repair kinetics, review, chromatin, complex damage

Citation Formats

Costes, Sylvain V, Chiolo, Irene, Pluth, Janice M, Barcellos-Hoff, Mary Helen, and Jakob, Burkhard. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization. United States: N. p., 2009. Web.
Costes, Sylvain V, Chiolo, Irene, Pluth, Janice M, Barcellos-Hoff, Mary Helen, & Jakob, Burkhard. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization. United States.
Costes, Sylvain V, Chiolo, Irene, Pluth, Janice M, Barcellos-Hoff, Mary Helen, and Jakob, Burkhard. 2009. "Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization". United States. https://www.osti.gov/servlets/purl/982831.
@article{osti_982831,
title = {Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization},
author = {Costes, Sylvain V and Chiolo, Irene and Pluth, Janice M and Barcellos-Hoff, Mary Helen and Jakob, Burkhard},
abstractNote = {DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.},
doi = {},
url = {https://www.osti.gov/biblio/982831}, journal = {Mutation Research},
issn = {0027-5107},
number = ,
volume = ,
place = {United States},
year = {Tue Sep 15 00:00:00 EDT 2009},
month = {Tue Sep 15 00:00:00 EDT 2009}
}