Chromosome band 11q23 translocation breakpoints are DNA topoisomerase II cleavage sites.
Human leukemias with 11q23 translocations occur sporadically and after cancer treatment with DNA topoisomerase II-targeted drugs. To investigate this process, we examined DNA topoisomerase II cleavage in vitro in subclones of the normal 11q23 genomic homologue and a t(9;11) translocation breakpoint junction. Cleavage was assayed with limiting dilutions of enzyme in the presence or absence of epipodophyllotoxin and ATP. The strongest sites of cleavage coincided with the t(9;11) breakpoint site and two other translocation breakpoint sites within the normal homologue. These results support the involvement of DNA topoisomerase II in the translocation process at chromosome band 11q23.
Felix
C A
CA
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Pennsylvania 19104, USA.
Lange
B J
BJ
Hosler
M R
MR
Fertala
J
J
Bjornsti
M A
MA
D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002899:Chromosomes, Human, Pair 9; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D004250:DNA Topoisomerases, Type II