Influence of nuclear structure on the formation of radiation-induced lethal lesions

Purpose The rejoining of fragmented nuclear DNA caused by ionizing radiation may lead to lethal chromosome rearrangements, such as rings or dicentrics. The clinically useful linear quadratic relationship between dose and cell survival has been interpreted as the generation of lethal lesions secondar...

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Vydané v:	International journal of radiation biology Ročník 92; číslo 5; s. 229 - 240
Hlavní autori:	Friedman, Daniel A., Tait, Lauren, Vaughan, Andrew T. M.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England Taylor & Francis 03.05.2016
Predmet:	Animals Apoptosis - genetics Apoptosis - radiation effects Cell Nucleus - physiology Cell Nucleus - radiation effects Cellular radiobiology chromosome abberations Chromosome Aberrations - radiation effects Computer Simulation DNA - genetics DNA - radiation effects DNA Damage - physiology Dose-Response Relationship, Radiation double-strand breaks Evidence-Based Medicine Humans microdosimetry models of cell killing Models, Genetic molecular radiobiology Radiation Dosage Cellular radiobiology microdosimetry chromosome abberations molecular radiobiology double-strand breaks models of cell killing
ISSN:	0955-3002, 1362-3095, 1362-3095
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Shrnutí:	Purpose The rejoining of fragmented nuclear DNA caused by ionizing radiation may lead to lethal chromosome rearrangements, such as rings or dicentrics. The clinically useful linear quadratic relationship between dose and cell survival has been interpreted as the generation of lethal lesions secondary to damage occurring in two separate chromosomes simultaneously (α component), or as potentially repairable separate events (β component). Here, the generation of such lesions is discussed, synthesizing existing knowledge with new insights gleaned from spatial proximity data made possible by high-throughput sequencing of chromosome conformation capture experiments. Over a range of several Mbp, the linear DNA strand is organized as a fractal globule generating multiple sites of contact that may facilitate deletions or inversions if the points of contact are damaged. On a larger scale, transcriptionally active euchromatin occupies a physically identifiable space separate from inactive areas and is preferentially susceptible to free radical attack after irradiation. Specific transcriptional programs link genomic locations within that space, potentially enhancing their interaction if subject to simultaneous fragmentation by a single radiation event. Conclusions High throughput spatial analysis of the factors that control chromosome proximity has the potential to better describe the formation of the lethal chromosome aberrations that kill irradiated cells.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	0955-3002 1362-3095 1362-3095
DOI:	10.3109/09553002.2016.1144941