[Illegitimate recombination as a possible mechanism of DNA-topoisomerase II induced chromosomal rearrangements].
Using semi-quantitative PCR-based approach, we have shown that the breakpoint cluster region of the AML1 gene was associated with the nuclear matrix. We have demonstrated that inhibition of topoisomerase II by etoposide stimulates the appearance of histone gammaH2AX foci, an indicator for the presence of DNA double-strand breaks. Furthermore, the major part of these foci was associated with the nuclear matrix. We also visualized nuclear matrix--associated multiprotein complexes involved in topoisomerase II--induced DNA double-strand break repair. Colocalization studies have demonstrated that these complexes included the principal components of the non-homologous end joining repair system (Ku80, DNA-PKcs and DNA ligase IV). Thus, it is reasonable to suggest that the non-homologous DNA end joining is a possible mechanism of topoisomerase II--induced chromosomal rearrangements.
Kantidze
O L
OL
Iarovaia
O V
OV
Klochkov
D B
DB
Razin
S V
SV
D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006657:Histones / Q000235:genetics; D006801:Humans; D000072200:Ku Autoantigen; D015530:Nuclear Matrix / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D059005:Topoisomerase II Inhibitors
D034961:Antigens, Nuclear; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; C000607893:LIG4 protein, human; C493728:RUNX1 protein, human; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004247:DNA; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D004250:DNA Topoisomerases, Type II; D011088:DNA Ligases; D000072481:DNA Ligase ATP