Effects of higher-order nuclear structure and Rad51 overexpression on radiation-induced chromosome rearrangements.
The microchromosomes (MICs) in chicken DT40 lymphocytes are usually clustered in the center of the nucleus, whereas the macrochromosomes (MACs) are preferentially located toward the nuclear periphery. This compartmentalized architecture of the nucleus is associated with a low frequency of translocations between MICs and MACs after induction of DNA breaks by a radiation track(s). In contrast, the MICs in chick embryo fibroblasts (CEFs) tend to be located throughout the entire nuclear volume. The resulting side-to-side arrangement of MIC and MAC territories favors radiation-induced MIC/MAC translocations, which occur more frequently in CEF cells than MIC/MIC or MAC/MAC rearrangements. Collectively, our results suggest that preformed physical contacts are a prerequisite for the generation of chromosome rearrangements through recombinational repair of DNA damage. Cell type-specific higher-order nuclear organization may prevent or stimulate the formation of particular chromosome aberrations in pathology and evolution. Ectopic expression of the recombination protein Rad51 can protect cells from radiation-induced translocations. The repair activity of overexpressed Rad51 is more important for cells that are irradiated in S/G(2) phase than for cells in G(1) phase. Evidently, homologous recombination between sister chromatids of a replicated chromosome is more frequent than that between homologous or heterologous chromosomes during G(1) phase.
Grandy
I
I
Charité Institute for Medical Genetics, Humboldt University, Berlin, Germany.
Hardt
T
T
Schmid
M
M
Haaf
T
T
D000818:Animals; D030161:Avian Proteins; D002478:Cells, Cultured; D002645:Chickens; D002875:Chromosomes / Q000528:radiation effects; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects; D015321:Gene Rearrangement; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D051135:Rad51 Recombinase; D011839:Radiation, Ionizing; D014162:Transfection; D014178:Translocation, Genetic
D030161:Avian Proteins; D004268:DNA-Binding Proteins; C495150:RAD51 protein, Gallus gallus; C495153:RAD51 protein, human; D051135:Rad51 Recombinase