Illegitimate recombination as a possible mechanism of topoisomerase-II-induced chromosomal rearrangements |
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Authors: | O. L. Kantidze O. V. Iarovaia D. B. Klochkov S. V. Razin |
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Affiliation: | (1) Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia;(2) Faculty of Biology, Moscow State University, Moscow, 119992, Russia |
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Abstract: | Using a semiquantitative PCR-based approach, a breakpoint cluster region of AML1 was associated with the nuclear matrix. Inhibition of topoisomerase II (topoII) by etoposide stimulated the appearance of histone γH2AX foci, indicative of DNA double-strand breaks (DSBs). The majority of these foci were associated with the nuclear matrix. Nuclear matrix-associated multiprotein complexes involved in topoII-induced DNA DSB repair were visualized. Colocalization studies demonstrated that these complexes included the main components of the nonhomologous end joining repair system (Ku80, DNA-PKcs, and DNA ligase IV). Thus, it was suggested that nonhomologous DNA end joining is a possible mechanism of topoII-induced chromosomal rear-rangements. |
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Keywords: | DNA double-strand breaks illegitimate recombination DNA topoisomerase II nuclear matrix |
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