Chemotherapy-related secondary leukemias: A role for DNA repair by error-prone non-homologous end joining in topoisomerase II - Induced chromosomal rearrangements.
Chromosome rearrangements are believed to cause the secondary leukemias which constitute frequent complications of antitumor chemotherapy with topoisomerase II-specific drugs. Here we show that inhibition of DNA topoisomerase II in cultured cells stimulates association of components of the non-homologous end joining system with a known breakpoint cluster region of the human AML1 gene, suggesting that errors of DNA repair during NHEJ may be the cause of illegitimate recombination in cells treated with topoisomerase II poisons.
Kantidze
Omar L
OL
Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology RAS, 34/5 Vavilov Street, 119334 Moscow, Russia.
Razin
Sergey V
SV
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D047369:Chromatin Immunoprecipitation; D002869:Chromosome Aberrations / Q000139:chemically induced*; D019457:Chromosome Breakage / Q000187:drug effects; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding / Q000187:drug effects; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D011995:Recombination, Genetic / Q000187:drug effects; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D050676:Core Binding Factor Alpha 2 Subunit; C497194:RAD52 protein, human; C493728:RUNX1 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004250:DNA Topoisomerases, Type II