Dependence of radiation-induced H2AX phosphorylation on histone methylation: Evidence from the chromatin immunoprecipitation assay

Sak, Ali; Kübler, Dennis; Bannik, Kristina; Groneberg, Michael; Stuschke, Martin

doi:10.3109/09553002.2015.997895

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…The packaging degree of the DNA has consequences for the repair process. This is especially true for the densely packed heterochromatin because the damaged DNA has to be histone free for the repair and must also be accessible for the repair protein complexes [46,47,48]. It has been shown that DSBs in the heterochromatin region are usually be repaired at the border of heterochromatic chromatin regions [1,2,14,49] whereby the methylation degree typical for heterochromatin remains unchanged.…”

Section: Introductionmentioning

confidence: 99%

Using Persistent Homology as a New Approach for Super-Resolution Localization Microscopy Data Analysis and Classification of γH2AX Foci/Clusters

Hofmann

Krufczik

Heermann

et al. 2018

IJMS

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DNA double strand breaks (DSB) are the most severe damages in chromatin induced by ionizing radiation. In response to such environmentally determined stress situations, cells have developed repair mechanisms. Although many investigations have contributed to a detailed understanding of repair processes, e.g., homologous recombination repair or non-homologous end-joining, the question is not sufficiently answered, how a cell decides to apply a certain repair process at a certain damage site, since all different repair pathways could simultaneously occur in the same cell nucleus. One of the first processes after DSB induction is phosphorylation of the histone variant H2AX to γH2AX in the given surroundings of the damaged locus. Since the spatial organization of chromatin is not random, it may be conclusive that the spatial organization of γH2AX foci is also not random, and rather, contributes to accessibility of special repair proteins to the damaged site, and thus, to the following repair pathway at this given site. The aim of this article is to demonstrate a new approach to analyze repair foci by their topology in order to obtain a cell independent method of categorization. During the last decade, novel super-resolution fluorescence light microscopic techniques have enabled new insights into genome structure and spatial organization on the nano-scale in the order of 10 nm. One of these techniques is single molecule localization microscopy (SMLM) with which the spatial coordinates of single fluorescence molecules can precisely be determined and density and distance distributions can be calculated. This method is an appropriate tool to quantify complex changes of chromatin and to describe repair foci on the single molecule level. Based on the pointillist information obtained by SMLM from specifically labeled heterochromatin and γH2AX foci reflecting the chromatin morphology and repair foci topology, we have developed a new analytical methodology of foci or foci cluster characterization, respectively, by means of persistence homology. This method allows, for the first time, a cell independent comparison of two point distributions (here the point distributions of two γH2AX clusters) with each other of a selected ensample and to give a mathematical measure of their similarity. In order to demonstrate the feasibility of this approach, cells were irradiated by low LET (linear energy transfer) radiation with different doses and the heterochromatin and γH2AX foci were fluorescently labeled by antibodies for SMLM. By means of our new analysis method, we were able to show that the topology of clusters of γH2AX foci can be categorized depending on the distance to heterochromatin. This method opens up new possibilities to categorize spatial organization of point patterns by parameterization of topological similarity.

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Section: Introductionmentioning

confidence: 99%

Using Persistent Homology as a New Approach for Super-Resolution Localization Microscopy Data Analysis and Classification of γH2AX Foci/Clusters

Hofmann

Krufczik

Heermann

et al. 2018

IJMS

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“…In mice, radiation exposure led to decreased trimethylation of histone H4 lysine which might result in relaxed heterochromatin organisation and would impair genome stability [26] . It has been shown in human cells that euchromatic regions were more susceptible to radiation-induced DNA damage and γH2AX accumulation [58][59][60] .…”

Section: Chromatin Remodelling and Radiationmentioning

confidence: 99%

The Role of Epigenetic Modulation in the Cellular Response to Ionizing Radiation

Pan

2015

International Journal of Radiology

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More and more evidence demonstrate that epigenetic modulation plays important roles in many cellular processes and carcinogenesis. It also showed that epigenetic changes are involved in the cellular response to ionizing radiation. In current review, we will discuss the radiation-induced epigenetic modifications including DNA methylation changes, chromatin remodelling and alterations in microRNA expression, and their roles in the cellular response to ionizing radiation. The aim is to help understand the mechanisms underlying the radiation induced biological effects in cells and to find the future research interests.

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“…Accumulations of the oxidative stresses and persistent pro-inflammatory responses cooperatively alters the cellular and mitochondrial redox balance, forms oxidized nucleotides, and impairs the DNA repair capacity, which results in DNA damages ( Dąbrowska and Wiczkowski, 2017 ; Czarny et al, 2018 ; Moloney and Cotter, 2018 ). Previous studies showed that genes in euchromatic regions were more susceptible to both HDR‐ and LDR-induced DNA damage, double-strand break, and r-H2AX accumulation ( Puck et al, 2002 ; Lafon-Hughes et al, 2008 ; Sak et al, 2015 ). Therefore, LDR-induced stresses convergently led to the permanent changes in the cells.…”

Section: Introductionmentioning

confidence: 99%

Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review

et al. 2020

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Ionizing radiation (IR) is a high-energy radiation whose biological effects depend on the irradiation doses. Low-dose radiation (LDR) is delivered during medical diagnoses or by an exposure to radioactive elements and has been linked to the occurrence of chronic diseases, such as leukemia and cardiovascular diseases. Though epidemiological research is indispensable for predicting and dealing with LDR-induced abnormalities in individuals exposed to LDR, little is known about epidemiological markers of LDR exposure. Moreover, difference in the LDR-induced molecular events in each organ has been an obstacle to a thorough investigation of the LDR effects and a validation of the experimental results in in vivo models. In this review, we summarized the recent reports on LDR-induced risk of organ-specifically arranged the alterations for a comprehensive understanding of the biological effects of LDR. We suggested that LDR basically caused the accumulation of DNA damages, controlled systemic immune systems, induced oxidative damages on peripheral organs, and even benefited the viability in some organs. Furthermore, we concluded that understanding of organ-specific responses and the biological markers involved in the responses is needed to investigate the precise biological effects of LDR.

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Dependence of radiation-induced H2AX phosphorylation on histone methylation: Evidence from the chromatin immunoprecipitation assay

Abstract: These data strengthen the dependence of IR-induced DNA damage response on the chromatin region.

Cited by 6 publications

References 36 publications

Using Persistent Homology as a New Approach for Super-Resolution Localization Microscopy Data Analysis and Classification of γH2AX Foci/Clusters

Using Persistent Homology as a New Approach for Super-Resolution Localization Microscopy Data Analysis and Classification of γH2AX Foci/Clusters

The Role of Epigenetic Modulation in the Cellular Response to Ionizing Radiation

Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review

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