Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;6).
Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (>70%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding affinity of each motif showed considerable differences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. Considering the high incidence and specific binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas.
Hosaka
T
T
Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Japan.
Kanoe
H
H
Nakayama
T
T
Murakami
H
H
Yamamoto
H
H
Nakamata
T
T
Tsuboyama
T
T
Oka
M
M
Kasai
M
M
Sasaki
M S
MS
Nakamura
T
T
Toguchida
J
J
D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D019457:Chromosome Breakage; D002881:Chromosomes, Human, Pair 12; D002885:Chromosomes, Human, Pair 16; D016384:Consensus Sequence; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034702:RNA-Binding Protein FUS; D013379:Substrate Specificity; D051742:Transcription Factor CHOP; D014178:Translocation, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; C106030:TLS-CHOP fusion protein, human; C095563:TSN protein, human; D051742:Transcription Factor CHOP