title: Competition effect in DNA damage response.
abstract: 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.
authors.affiliation: LRT2, Universität der Bundeswehr München, 85579 Neubiberg, Germany. christoph.greubel@unibw.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Greubel
authors.forename: Volker
authors.initials: V
authors.lastname: Hable
authors.forename: Guido A
authors.initials: GA
authors.lastname: Drexler
authors.forename: Andreas
authors.initials: A
authors.lastname: Hauptner
authors.forename: Steffen
authors.initials: S
authors.lastname: Dietzel
authors.forename: Hilmar
authors.initials: H
authors.lastname: Strickfaden
authors.forename: Iris
authors.initials: I
authors.lastname: Baur
authors.forename: Reiner
authors.initials: R
authors.lastname: Krücken
authors.forename: Thomas
authors.initials: T
authors.lastname: Cremer
authors.forename: Günther
authors.initials: G
authors.lastname: Dollinger
authors.forename: Anna A
authors.initials: AA
authors.lastname: Friedl
mesh_terms: D004247:DNA / Q000528:radiation effects* / Q000648:ultrastructure; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*; D011829:Radiation Dosage
chemical_list: D004247:DNA