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

Sci Rep. 2013:3:2511. doi: 10.1038/srep02511.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Chromatin / chemistry*
  • Chromatin / genetics
  • DNA Damage / genetics*
  • DNA Repair / genetics*
  • DNA, Neoplasm / chemistry*
  • DNA, Neoplasm / genetics*
  • Diffusion
  • Humans
  • Models, Genetic
  • Models, Statistical
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics*
  • Osteosarcoma / chemistry
  • Osteosarcoma / genetics
  • Protein Binding
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Chromatin
  • DNA, Neoplasm
  • MDC1 protein, human
  • Nuclear Proteins
  • Trans-Activators