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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

Histogram of distance changes (Δl(Δt = 60 s) between two neighbouring foci after carbon irradiation, fitted with the distribution function for normal and anomalous diffusion on linear (A) and logarithmic scale (B) (bin size = 0.03 μm, number of data points Ntotal = 5656).SE-error bars are taken as  given through Poisson statistics.
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f3: Histogram of distance changes (Δl(Δt = 60 s) between two neighbouring foci after carbon irradiation, fitted with the distribution function for normal and anomalous diffusion on linear (A) and logarithmic scale (B) (bin size = 0.03 μm, number of data points Ntotal = 5656).SE-error bars are taken as given through Poisson statistics.

Mentions: The anomality of the diffusion of MDC1 foci can also be recognized in the histogram of distance changes Δli for a single time interval Δt obtained for the carbon-irradiated samples (Fig. 3). Normal diffusion would lead to a Gaussian distribution of the probability density p(Δl, Δt) of the Δli(Δt) values for initial distances much larger than the diffusional length20. The measured distribution function differs significantly from a Gaussian distribution, but is well fitted by the distribution function for subdiffusion (adapted from20) when using an anomalous diffusion exponent α = 0.5 (see Fig. 3, where Δt = 60 s) and applying a two dimensional random walk situation for distance analysis and thus substituting x → Δl and Kα → 2dDα: The differences to the Gaussian are visible both at very small distances, where a cusp-shaped histogram is obtained as predicted by the subdiffusion model (see plot on linear scale of Fig. 3a), as well as in the tails, where the distributions are significantly higher than predicted by a best Gaussian fit (log-plot of Fig. 3b). We conclude from our live-cell imaging and distance tracking over time periods between a few seconds and several hours after irradiation that IRIF do not diffuse normally but follow a subdiffusion process.


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)

Histogram of distance changes (Δl(Δt = 60 s) between two neighbouring foci after carbon irradiation, fitted with the distribution function for normal and anomalous diffusion on linear (A) and logarithmic scale (B) (bin size = 0.03 μm, number of data points Ntotal = 5656).SE-error bars are taken as  given through Poisson statistics.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Histogram of distance changes (Δl(Δt = 60 s) between two neighbouring foci after carbon irradiation, fitted with the distribution function for normal and anomalous diffusion on linear (A) and logarithmic scale (B) (bin size = 0.03 μm, number of data points Ntotal = 5656).SE-error bars are taken as given through Poisson statistics.
Mentions: The anomality of the diffusion of MDC1 foci can also be recognized in the histogram of distance changes Δli for a single time interval Δt obtained for the carbon-irradiated samples (Fig. 3). Normal diffusion would lead to a Gaussian distribution of the probability density p(Δl, Δt) of the Δli(Δt) values for initial distances much larger than the diffusional length20. The measured distribution function differs significantly from a Gaussian distribution, but is well fitted by the distribution function for subdiffusion (adapted from20) when using an anomalous diffusion exponent α = 0.5 (see Fig. 3, where Δt = 60 s) and applying a two dimensional random walk situation for distance analysis and thus substituting x → Δl and Kα → 2dDα: The differences to the Gaussian are visible both at very small distances, where a cusp-shaped histogram is obtained as predicted by the subdiffusion model (see plot on linear scale of Fig. 3a), as well as in the tails, where the distributions are significantly higher than predicted by a best Gaussian fit (log-plot of Fig. 3b). We conclude from our live-cell imaging and distance tracking over time periods between a few seconds and several hours after irradiation that IRIF do not diffuse normally but follow a subdiffusion process.

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