Double-strand breaks (DSBs), continuously introduced into DNA by cell metabolism, ionizing radiation and some chemicals, are the biologically most deleterious type of genome damage, and must be accurately repaired to protect genomic integrity, ensure cell survival, and prevent carcinogenesis. Although a huge amount of information has been published on the molecular basis and biological significance of DSB repair, our understanding of DSB repair and its spatiotemporal arrangement is still incomplete. In particular, the role of higher-order chromatin structure in DSB induction and repair, movement of DSBs and the mechanism giving rise to chromatin exchanges, and many other currently disputed questions are discussed in this review. Finally, a model explaining the formation of chromosome translocations is proposed.

• MeSH
• Models, Biological MeSH
• Chromatin radiation effects   ultrastructure   MeSH
• DNA Breaks, Double-Stranded * MeSH
• Radiation, Ionizing * MeSH
• Humans MeSH
• DNA Repair * MeSH
• DNA Damage MeSH
• Translocation, Genetic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Chromatin MeSH

Cell differentiation is associated with extensive gene silencing, heterochromatinization and potentially decreasing need for repairing DNA double-strand breaks (DSBs). Differentiation stages of blood cells thus represent an excellent model to study DSB induction, repair and misrepair in the context of changing higher-order chromatin structure. We show that immature granulocytes form γH2AX and 53BP1 foci, contrary to the mature cells; however, these foci colocalize only rarely and DSB repair is inefficient. Moreover, specific chromatin structure of granulocytes probably influences DSB induction.

• Keywords
• Chromatin sensitivity to DSB induction, DNA double strand break (DSB) repair, Heterochromatin, Higher-order chromatin structure, Immature and terminally differentiated granulocytes, γH2AX/53BP1 repair foci,
• MeSH
• Cell Differentiation * MeSH
• Chromatin chemistry   MeSH
• In Situ Hybridization, Fluorescence MeSH
• Protein Conformation MeSH
• Cells, Cultured MeSH
• Humans MeSH
• DNA Repair * MeSH
• DNA Damage * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chromatin MeSH

According to their physical characteristics, protons and ion beams promise a revolution in cancer radiotherapy. Curing protocols however reflect rather the empirical knowledge than experimental data on DNA repair. This especially holds for the spatio-temporal organization of repair processes in the context of higher-order chromatin structure-the problematics addressed in this work. The consequences for the mechanism of chromosomal translocations are compared for gamma rays and proton beams.

• Keywords
• DNA double-strand breaks (DSBs), Formation of chromosomal translocations, Gamma rays and proton beams, Higher-order chromatin structure and DSB repair, γH2AX foci,
• MeSH
• Cell Nucleus radiation effects   MeSH
• Chromatin chemistry   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Microscopy MeSH
• DNA Repair * MeSH
• DNA Damage * MeSH
• Protons * MeSH
• Translocation, Genetic MeSH
• Gamma Rays * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chromatin MeSH
• Protons * MeSH