title: Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci.
abstract: Carbon ion radiation is a promising new form of radiotherapy for cancer, but the central question about the biologic effects of charged particle radiation is yet incompletely understood. Key to this question is the understanding of the interaction of ions with DNA in the cell's nucleus. Induction and repair of DNA lesions including double-strand breaks (DSBs) are decisive for the cell. Several DSB repair markers have been used to investigate these processes microscopically, but the limited resolution of conventional microscopy is insufficient to provide structural insights. We have applied superresolution microscopy to overcome these limitations and analyze the fine structure of DSB repair foci. We found that the conventionally detected foci of the widely used DSB marker γH2AX (Ø 700-1000 nm) were composed of elongated subfoci with a size of ∼100 nm consisting of even smaller subfocus elements (Ø 40-60 nm). The structural organization of the subfoci suggests that they could represent the local chromatin structure of elementary DSB repair units at the DSB damage sites. Subfocus clusters may indicate induction of densely spaced DSBs, which are thought to be associated with the high biologic effectiveness of carbon ions. Superresolution microscopy might emerge as a powerful tool to improve our knowledge of interactions of ionizing radiation with cells.-Lopez Perez, R., Best, G., Nicolay, N. H., Greubel, C., Rossberger, S., Reindl, J., Dollinger, G., Weber, K.-J., Cremer, C., Huber, P. E. Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci.
authors.affiliation: Clinical Cooperation Unit and Molecular Radiation Oncology, German Cancer Research Center, Heidelberg University Hospital, Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; r.lopez@dkfz.de.
authors.forename: Ramon
authors.initials: R
authors.lastname: Lopez Perez
authors.affiliation: Department of Ophthalmology, Heidelberg University Hospital, Heidelberg, Germany; Kirchhoff-Institute for Physics, Heidelberg University, Heidelberg, Germany;
authors.forename: Gerrit
authors.initials: G
authors.lastname: Best
authors.affiliation: Clinical Cooperation Unit and Molecular Radiation Oncology, German Cancer Research Center, Heidelberg University Hospital, Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany;
authors.forename: Nils H
authors.initials: NH
authors.lastname: Nicolay
authors.affiliation: Institut für Angewandte Physik und Messtechnik, Universität der Bundeswehr München, Neubiberg, Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Greubel
authors.affiliation: Kirchhoff-Institute for Physics, Heidelberg University, Heidelberg, Germany;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossberger
authors.affiliation: Institut für Angewandte Physik und Messtechnik, Universität der Bundeswehr München, Neubiberg, Germany; and.
authors.forename: Judith
authors.initials: J
authors.lastname: Reindl
authors.affiliation: Institut für Angewandte Physik und Messtechnik, Universität der Bundeswehr München, Neubiberg, Germany; and.
authors.forename: Günther
authors.initials: G
authors.lastname: Dollinger
authors.affiliation: Clinical Cooperation Unit and Molecular Radiation Oncology, German Cancer Research Center, Heidelberg University Hospital, Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany;
authors.forename: Klaus-Josef
authors.initials: KJ
authors.lastname: Weber
authors.affiliation: Kirchhoff-Institute for Physics, Heidelberg University, Heidelberg, Germany; Superresolution Microscopy of Functional Nuclear Nanostructure, Institute of Molecular Biology, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Cremer
authors.affiliation: Clinical Cooperation Unit and Molecular Radiation Oncology, German Cancer Research Center, Heidelberg University Hospital, Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; p.huber@dkfz.de.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
mesh_terms: D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology*; D005786:Gene Expression Regulation; D063193:Heavy Ion Radiotherapy; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008853:Microscopy / Q000379:methods*
chemical_list: C468783:H2AX protein, human; D006657:Histones
keywords: heavy ion radiation; nanoscopy; γH2AX