Competition effect in DNA damage response

Radiat Environ Biophys. 2008 Nov;47(4):423-9. doi: 10.1007/s00411-008-0182-z. Epub 2008 Jul 23.


We have built an ion-microbeam for studies of the nuclear topography and kinetics of double-strand break repair at the single cell level. Here, we show that a first and a second, delayed single ion exposure at different nuclear sites led to comparable accumulations of phospho-ATM, gamma-H2AX and Mdc1 at both earlier (e) and later (l) microirradiated sites. In contrast, accumulations of 53BP1 and the recombination protein Rad51 were strongly reduced at l-sites. This apparent competition effect is accompanied by a reduced amount of 53BP1 in undamaged areas of the irradiated nuclei. We suggest that a critically limited pool size combined with strong binding at irradiated sites leads to the exhaustion of unbound factors freely roaming the nuclear space. The undersupply of these factors at l-sites requires in addition a long-lasting binding at e-sites or a weaker binding at l-sites. The observed effects suggest that DNA damage response at individual nuclear sites depends on the time course of damage load. This may have implications for therapeutic radiation treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / radiation effects*
  • DNA / ultrastructure
  • DNA Damage / physiology*
  • DNA Repair / physiology*
  • DNA Repair / radiation effects*
  • Dose-Response Relationship, Radiation
  • Humans
  • Microscopy, Fluorescence / methods*
  • Radiation Dosage


  • DNA