Subdiffusion Supports Joining Of Correct Ends During Repair Of DNA Double-Strand Breaks

• Published in: Scientific reports 2013-08, Vol.3 (1), p.2511-2511, Article 2511
• Main Authors: Girst, S., Hable, V., Drexler, G. A., Greubel, C., Siebenwirth, C., Haum, M., Friedl, A. A., Dollinger, G.
• Format: Article
• Language: English
• Subjects: 631/208; 631/57; 631/80; 639/766/530; Cell Line, Tumor; Chromatin; Chromatin - chemistry; Chromatin - genetics; Chromosome aberrations; Chromosomes; Deoxyribonucleic acid; Diffusion; DNA; DNA damage; DNA Damage - genetics; DNA repair; DNA Repair - genetics; DNA, Neoplasm - chemistry; DNA, Neoplasm - genetics; Double-strand break repair; Humanities and Social Sciences; Humans; Irradiation; Models, Genetic; Models, Statistical; multidisciplinary; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclei; Osteosarcoma - chemistry; Osteosarcoma - genetics; Protein Binding; Radiation; Science; Trans-Activators - chemistry; Trans-Activators - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep02511

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.