Alternating purine-pyrimidine tracts may promote chromosomal translocations seen in a variety of human lymphoid tumours.
Chromosomal abnormalities which are prevalent in human lymphoid tumours are believed to be involved in tumour pathogenesis and their formation may be the result of erroneous activity by the V-D-J recombinase. Frequently, recombinase accessibility is provided by prior transcription of the chromosomal regions involved. However, this may not always be so and in those cases DNA structural features must be involved. Here we examine the breakpoints of three different tumour-specific translocations in the proximity of which we can detect no transcription; two of the translocations involve regions of chromosome 11, (t[11;14] [p13;q11] and t[11;14] [q13;q32]), and the third is a newly described translocation, t[7;10] [q35;q24], involving the T cell receptor beta-gene on chromosome 7. In each case, a purine--pyrimidine tract (potential Z-DNA) occurs near the translocation breakpoints. Four independent tumours with translocation t[11;14] [p13;q11] reveal a 2 kb breakpoint cluster region at 11p13 with an adjacent potential Z-DNA region of 62 bp in length; the analogous purine--pyrimidine tract at 10q24 is 32 bp long. The purine--pyrimidine tract at the 11q13 chromosome breakpoint, however, is very large as it covers approximately 800 bp. The position, surrounding sequence and potential Z-DNA tract of the human 11p13 TALLber is conserved in rodents. These results suggest that the purine--pyrimidine tracts, presumably in the Z-DNA form, can influence chromatin structure giving access for recombinase-mediated translocations. Such putative alterations of chromatin organization are supported by the observation of DNase I hypersensitive sites near to translocation breakpoints on 10q24 and 11p13.
Boehm
T
T
Laboratory of Molecular Biology, Cambridge, UK.
Mengle-Gaw
L
L
Kees
U R
UR
Spurr
N
N
Lavenir
I
I
Forster
A
A
Rabbitts
T H
TH
D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002843:Chromatin / Q000032:analysis; D006224:Cricetinae; D004254:DNA Nucleotidyltransferases; D004273:DNA, Neoplasm; D003850:Deoxyribonuclease I; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D045567:VDJ Recombinases
D002843:Chromatin; D004273:DNA, Neoplasm; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases; D003850:Deoxyribonuclease I