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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

Double-logarithmic plot of the squared standard deviations σ2 (±SEM) of the distance changes Δl(Δt) between neighbouring MDC1 foci in the nuclei of cells irradiated with carbon ions (filled squares, 657 foci pairs from 58 cells) and protons (open circles, 32 p per irradiation point, 99 foci pairs from 12 cells), each 30–60 time frames analyzed per sample.The data are fitted with the power-law function (eq. (2)).
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f4: Double-logarithmic plot of the squared standard deviations σ2 (±SEM) of the distance changes Δl(Δt) between neighbouring MDC1 foci in the nuclei of cells irradiated with carbon ions (filled squares, 657 foci pairs from 58 cells) and protons (open circles, 32 p per irradiation point, 99 foci pairs from 12 cells), each 30–60 time frames analyzed per sample.The data are fitted with the power-law function (eq. (2)).

Mentions: To investigate whether IRIF diffusion depends on the density of damage sites along the irradiation track, the cells were also irradiated in a matrix of Δx = Δy = 6 μm with 32 protons (20 MeV at cell position, linear energy transfer LET = 2.6 keV/μm) per point. The number of protons was chosen to create on average 3 DSB per matrix point so that within the depth of view each detected IRIF contained on average only one DSB, while after carbon irradiation several DSB are expected to occur in each IRIF. As in the case of carbon-irradiated cells, a linear increase of log(σ2) with log(Δt) is evident (Fig. 4), demonstrating a power-law dependence of σ2 on Δt. For comparison, also the data obtained after carbon ion irradiation are shown.


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)

Double-logarithmic plot of the squared standard deviations σ2 (±SEM) of the distance changes Δl(Δt) between neighbouring MDC1 foci in the nuclei of cells irradiated with carbon ions (filled squares, 657 foci pairs from 58 cells) and protons (open circles, 32 p per irradiation point, 99 foci pairs from 12 cells), each 30–60 time frames analyzed per sample.The data are fitted with the power-law function (eq. (2)).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Double-logarithmic plot of the squared standard deviations σ2 (±SEM) of the distance changes Δl(Δt) between neighbouring MDC1 foci in the nuclei of cells irradiated with carbon ions (filled squares, 657 foci pairs from 58 cells) and protons (open circles, 32 p per irradiation point, 99 foci pairs from 12 cells), each 30–60 time frames analyzed per sample.The data are fitted with the power-law function (eq. (2)).
Mentions: To investigate whether IRIF diffusion depends on the density of damage sites along the irradiation track, the cells were also irradiated in a matrix of Δx = Δy = 6 μm with 32 protons (20 MeV at cell position, linear energy transfer LET = 2.6 keV/μm) per point. The number of protons was chosen to create on average 3 DSB per matrix point so that within the depth of view each detected IRIF contained on average only one DSB, while after carbon irradiation several DSB are expected to occur in each IRIF. As in the case of carbon-irradiated cells, a linear increase of log(σ2) with log(Δt) is evident (Fig. 4), demonstrating a power-law dependence of σ2 on Δt. For comparison, also the data obtained after carbon ion irradiation are shown.

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