Preferential localization of γH2AX foci in euchromatin of retina rod cells after DNA damage induction

Lafon-Hughes, Laura; Tomaso, María Vittoria Di; Liddle, Pablo; Toledo, Andrea; Reyes-Ábalos, Ana Laura; Folle, Gustavo A.

doi:10.1007/s10577-013-9395-3

Cited by 11 publications

(15 citation statements)

References 61 publications

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“…Conversely, for alphas of 5.27 MeV, more DSB/kbp were observed in the euchromatin than in the heterochromatin, 0.0049 ± 0.0003 and 0.0045 ± 0.0004, respectively. Again, a time of 10 ns seems to be more suitable as it better reproduces the difference between condensed and decondensed chromatin, that is, more DSB damage in the euchromatin than in the heterochromatin as indicated in different studies …”

Section: Discussionmentioning

confidence: 99%

“…Among other functions, it is well known that chromatin compaction plays an essential role in DNA repair, and can influence the sensitivity to DNA damage . Indeed, it has been shown in previous studies that γ ‐H2AX foci, which are used as specific markers of DSB signaling, are more often located in euchromatin regions, which could imply that these regions are more susceptible to DNA damage . Other authors have even reported the role of chromatin compaction in the protection of DNA from radiation damage induction, to preserve genome integrity .…”

Section: Introductionmentioning

confidence: 99%

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Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Tang

Bueno

Meylan³

et al. 2019

Medical Physics

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Purpose In this work, we present simulated double‐strand breaks (DSBs) obtained for two human cell nucleus geometries. The first cell nucleus represents fibroblasts, filled with DNA molecules in different compaction forms: heterochromatin or euchromatin only. The second one represents an endothelial cell nucleus, either filled with heterochromatin only or with a uniform distribution of 48% of heterochromatin and 52% of euchromatin, obtained from measurements carried out at IRSN. Protons and alpha particles of different energies were used as projectiles. Each cell nucleus model includes a multi‐scale description of the DNA target from the molecular level to the whole human genome representation. Methods The cell nucleus models were generated using an extended version of the DnaFabric software in which a new model of euchromatin was implemented in addition to the existing model of heterochromatin. Thus, each nucleus model contains the complete human genome (a total of 6 Gbp) in the G0/G1 phase of the cycle, filled with a continuous chromatin fiber per chromosome that can take into account the heterochromatin and the euchromatin compaction. These geometries were then exported to a simulation chain using the Monte Carlo toolkit Geant4‐DNA to perform computations of the physical, physicochemical, and chemical stages, in order to evaluate the influence of chromatin compaction on DSB induction and the contribution of direct and indirect damage, as well as DSB complexity. Results More direct damage and less indirect damage were observed in the heterochromatin than in the euchromatin. Nevertheless, no difference in terms of DSB complexity was observed between those formed in the heterochromatin or the euchromatin models. Yields of DSB/Gy/Gbp show an increase when both heterochromatin and euchromatin models are taken into account, compared to when only heterochromatin is considered. Conclusions The results presented indicate that the chromatin compaction decreases DNA damage generated by ionizing radiation and thus, DNA compaction should be considered for the simulation of DNA repair and other cellular outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Tang

Bueno

Meylan³

et al. 2019

Medical Physics

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“…In addition, increased γ-H2AX foci formation occurs at a defined region of transcribed genes relative to a gene-poor region after irradiation (Falk et al 2008). Changes in histone modifications may also affect the progression of the DNA damage response (DDR) by interfering with the restoration of baseline chromatin structure after repair (Ayrapetov et al 2014;Burgess et al 2014;Khurana et al 2014), since, in ASH2L-expressing cells, recondensation at the site of DNA damage as well as upstream DDR signaling is dampened (Burgess et al 2014), and γ-H2AX foci formation after irradiation is associated with loss of H3K4me3 (Seiler et al 2011;Lafon-Hughes et al 2013;Maroschik et al 2014). These observations suggest that H3K4 hypermethylation may impair DDR progression by counteracting condensation and signaling required for efficient DDR, thus resulting in persistent DSBs and enhancing the likelihood of formation of translocations.…”

Section: Discussionmentioning

confidence: 99%

Histone modifications predispose genome regions to breakage and translocation

et al. 2015

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Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations.

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“…Notably, DNA DSBs in heterochromatin relocalize to euchromatic regions during repair (Jakob et al 2011), and as a consequence heterochromatic regions often appear to lack radiation-induced g-H2AX foci (Cowell et al 2007;Kim et al 2007;Goodarzi et al 2008;Vasireddy et al 2010;Chiolo et al 2011;Jakob et al 2011;Lafon-Hughes et al 2013). The relocalization of heterochromatin DSBs to the periphery of heterochromatic domains is accompanied by a transient ATM-dependent chromatin relaxation (Ziv et al 2006;Geuting et al 2013).…”

Section: Nuclear Compartmentsmentioning

confidence: 99%

Cell Biology of Mitotic Recombination

Lisby

Rothstein

2015

Cold Spring Harb Perspect Biol

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Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as well as the cellular organization of the process of homologous recombination. Herein we review the cell biological aspects of mitotic homologous recombination with a focus on Saccharomyces cerevisiae and mammalian cells, but will also draw on findings from other experimental systems. Key topics of this review include the stoichiometry and dynamics of recombination complexes in vivo, the choreography of assembly and disassembly of recombination proteins at sites of DNA damage, the mobilization of damaged DNA during homology search, and the functional compartmentalization of the nucleus with respect to capacity of homologous recombination.

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Preferential localization of γH2AX foci in euchromatin of retina rod cells after DNA damage induction

Cited by 11 publications

References 61 publications

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA

Histone modifications predispose genome regions to breakage and translocation

Cell Biology of Mitotic Recombination

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