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Subdiffusion supports joining of correct ends during repair of DNA double-strand breaks.

Girst S, Hable V, Drexler GA, Greubel C, Siebenwirth C, Haum M, Friedl AA, Dollinger G - Sci Rep (2013)

Bottom Line: Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation.As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair.It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.

View Article: PubMed Central - PubMed

Affiliation: Angewandte Physik und Messtechnik LRT2, Universität der Bundeswehr München, 85577 Neubiberg, Germany. stefanie.girst@unibw.de

ABSTRACT
The mobility of damaged chromatin regions in the nucleus may affect the probability of mis-repair. In this work, live-cell observation and distance tracking of GFP-tagged DNA damage response protein MDC1 was used to study the random-walk behaviour of chromatin domains containing radiation-induced DNA double-strand breaks (DSB). Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation. As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair. It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.

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Related in: MedlinePlus

U2OS cell irradiated with carbon ions in a 5 × 5 μm2 matrix pattern, visible under the fluorescence microscope by GFP-tagging of DNA repair protein MDC1 which accumulates at the radiation induced double-strand breaks (“foci”).The distance li between neighbouring foci is recorded at several time points tj for analyzing the distance changes Δli over different time intervals Δt.
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f1: U2OS cell irradiated with carbon ions in a 5 × 5 μm2 matrix pattern, visible under the fluorescence microscope by GFP-tagging of DNA repair protein MDC1 which accumulates at the radiation induced double-strand breaks (“foci”).The distance li between neighbouring foci is recorded at several time points tj for analyzing the distance changes Δli over different time intervals Δt.

Mentions: U2OS cells expressing GFP-tagged repair protein MDC1 were irradiated in a matrix pattern with single carbon (12C) ions per point. The distances li of adjacent MDC1 foci pairs numbered by i were monitored for several hours post-irradiation (Fig. 1). The distance changes Δli(Δt) during different time intervals Δt (i.e. Δli(Δt) = li(tj + Δt) − li(tj) for all time points tj of the time series) were determined.


Subdiffusion supports joining of correct ends during repair of DNA double-strand breaks.

Girst S, Hable V, Drexler GA, Greubel C, Siebenwirth C, Haum M, Friedl AA, Dollinger G - Sci Rep (2013)

U2OS cell irradiated with carbon ions in a 5 × 5 μm2 matrix pattern, visible under the fluorescence microscope by GFP-tagging of DNA repair protein MDC1 which accumulates at the radiation induced double-strand breaks (“foci”).The distance li between neighbouring foci is recorded at several time points tj for analyzing the distance changes Δli over different time intervals Δt.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3753591&req=5

f1: U2OS cell irradiated with carbon ions in a 5 × 5 μm2 matrix pattern, visible under the fluorescence microscope by GFP-tagging of DNA repair protein MDC1 which accumulates at the radiation induced double-strand breaks (“foci”).The distance li between neighbouring foci is recorded at several time points tj for analyzing the distance changes Δli over different time intervals Δt.
Mentions: U2OS cells expressing GFP-tagged repair protein MDC1 were irradiated in a matrix pattern with single carbon (12C) ions per point. The distances li of adjacent MDC1 foci pairs numbered by i were monitored for several hours post-irradiation (Fig. 1). The distance changes Δli(Δt) during different time intervals Δt (i.e. Δli(Δt) = li(tj + Δt) − li(tj) for all time points tj of the time series) were determined.

Bottom Line: Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation.As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair.It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.

View Article: PubMed Central - PubMed

Affiliation: Angewandte Physik und Messtechnik LRT2, Universität der Bundeswehr München, 85577 Neubiberg, Germany. stefanie.girst@unibw.de

ABSTRACT
The mobility of damaged chromatin regions in the nucleus may affect the probability of mis-repair. In this work, live-cell observation and distance tracking of GFP-tagged DNA damage response protein MDC1 was used to study the random-walk behaviour of chromatin domains containing radiation-induced DNA double-strand breaks (DSB). Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation. As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair. It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.

Show MeSH
Related in: MedlinePlus