Abstract
A reexamination of human minisatellite (hypervariable) regions following the cloning and sequencing of the new minisatellite, VTR1.1, revealed that many of these structures possessed a strongly conserved copy of the chi-like octamer, GC[A/T]GG[A/T]GG. In oncogene translocations apparently created by aberrant VDJ recombinase activity, this VTR octamer was often found within a few bases of the breakpoint (p less than 10(-10)). Three bcl2 rearrangements which occurred within 2 bp of one another were located precisely adjacent to this consensus; it defined the 5' border of that oncogene's major breakpoint cluster. Several c-myc translocations also occurred within 2 bp of this sequence. While the appearance of a chi-like element in polymorphic minisatellite sequences is consistent with a role promoting either recombination or replication slippage, the existence of such elements at sites of somatic translocations suggests chi function in site-specific recombination, perhaps as a subsidiary recognition signal in immunoglobulin gene rearrangement. We discuss the implications of these observations for mechanisms by which oncogene translocations and minisatellite sequences are generated.
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- Azen E., Lyons K. M., McGonigal T., Barrett N. L., Clements L. S., Maeda N., Vanin E. F., Carlson D. M., Smithies O. Clones from the human gene complex coding for salivary proline-rich proteins. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5561–5565. doi: 10.1073/pnas.81.17.5561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bakhshi A., Wright J. J., Graninger W., Seto M., Owens J., Cossman J., Jensen J. P., Goldman P., Korsmeyer S. J. Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2396–2400. doi: 10.1073/pnas.84.8.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boehm T., Buluwela L., Williams D., White L., Rabbitts T. H. A cluster of chromosome 11p13 translocations found via distinct D-D and D-D-J rearrangements of the human T cell receptor delta chain gene. EMBO J. 1988 Jul;7(7):2011–2017. doi: 10.1002/j.1460-2075.1988.tb03040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleary M. L., Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. doi: 10.1073/pnas.82.21.7439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
- Colb M., Yang-Feng T., Francke U., Mermer B., Parkinson D. R., Krontiris T. G. A variable tandem repeat locus mapped to chromosome band 10q26 is amplified and rearranged in leukocyte DNAs of two cancer patients. Nucleic Acids Res. 1986 Oct 24;14(20):7929–7937. doi: 10.1093/nar/14.20.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dalla-Favera R., Martinotti S., Gallo R. C., Erikson J., Croce C. M. Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science. 1983 Feb 25;219(4587):963–967. doi: 10.1126/science.6401867. [DOI] [PubMed] [Google Scholar]
- Dyson P. J., Rabbitts T. H. Chromatin structure around the c-myc gene in Burkitt lymphomas with upstream and downstream translocation points. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1984–1988. doi: 10.1073/pnas.82.7.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eckert R. L., Green H. Structure and evolution of the human involucrin gene. Cell. 1986 Aug 15;46(4):583–589. doi: 10.1016/0092-8674(86)90884-6. [DOI] [PubMed] [Google Scholar]
- Gauwerky C. E., Haluska F. G., Tsujimoto Y., Nowell P. C., Croce C. M. Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548–8552. doi: 10.1073/pnas.85.22.8548. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gelmann E. P., Psallidopoulos M. C., Papas T. S., Dalla-Favera R. Identification of reciprocal translocation sites within the c-myc oncogene and immunoglobulin mu locus in a Burkitt lymphoma. Nature. 1983 Dec 22;306(5945):799–803. doi: 10.1038/306799a0. [DOI] [PubMed] [Google Scholar]
- Georges M., Lequarré A. S., Castelli M., Hanset R., Vassart G. DNA fingerprinting in domestic animals using four different minisatellite probes. Cytogenet Cell Genet. 1988;47(3):127–131. doi: 10.1159/000132529. [DOI] [PubMed] [Google Scholar]
- Haluska F. G., Tsujimoto Y., Croce C. M. The t(8;14) breakpoint of the EW 36 undifferentiated lymphoma cell line lies 5' of MYC in a region prone to involvement in endemic Burkitt's lymphomas. Nucleic Acids Res. 1988 Mar 25;16(5):2077–2085. doi: 10.1093/nar/16.5.2077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haluska F. G., Tsujimoto Y., Croce C. M. The t(8;14) chromosome translocation of the Burkitt lymphoma cell line Daudi occurred during immunoglobulin gene rearrangement and involved the heavy chain diversity region. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6835–6839. doi: 10.1073/pnas.84.19.6835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hollis G. F., Mitchell K. F., Battey J., Potter H., Taub R., Lenoir G. M., Leder P. A variant translocation places the lambda immunoglobulin genes 3' to the c-myc oncogene in Burkitt's lymphoma. Nature. 1984 Feb 23;307(5953):752–755. doi: 10.1038/307752a0. [DOI] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Kelly R., Taylor B. A., Bulfield G. Mouse DNA 'fingerprints': analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains. Nucleic Acids Res. 1987 Apr 10;15(7):2823–2836. doi: 10.1093/nar/15.7.2823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Thein S. L. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. doi: 10.1038/314067a0. [DOI] [PubMed] [Google Scholar]
- Kasperczyk A., Mermer B. A., Parkinson D. R., Lonergan J. A., Krontiris T. G. Allele-specific deletion in exon I of the HRAS1 gene. Am J Hum Genet. 1989 Nov;45(5):689–696. [PMC free article] [PubMed] [Google Scholar]
- Kenter A. L., Birshtein B. K. Chi, a promoter of generalized recombination in lambda phage, is present in immunoglobulin genes. Nature. 1981 Oct 1;293(5831):402–404. doi: 10.1038/293402a0. [DOI] [PubMed] [Google Scholar]
- Kominami R., Mitani K., Muramatsu M. Nucleotide sequence of a mouse minisatellite DNA. Nucleic Acids Res. 1988 Feb 11;16(3):1197–1197. doi: 10.1093/nar/16.3.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ludwig E. H., Friedl W., McCarthy B. J. High-resolution analysis of a hypervariable region in the human apolipoprotein B gene. Am J Hum Genet. 1989 Sep;45(3):458–464. [PMC free article] [PubMed] [Google Scholar]
- Moulding C., Rapoport A., Goldman P., Battey J., Lenoir G. M., Leder P. Structural analysis of both products of a reciprocal translocation between c-myc and immunoglobulin loci in Burkitt lymphoma. Nucleic Acids Res. 1985 Mar 25;13(6):2141–2152. doi: 10.1093/nar/13.6.2141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
- Saito H., Hayday A. C., Wiman K., Hayward W. S., Tonegawa S. Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7476–7480. doi: 10.1073/pnas.80.24.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Showe L. C., Ballantine M., Nishikura K., Erikson J., Kaji H., Croce C. M. Cloning and sequencing of a c-myc oncogene in a Burkitt's lymphoma cell line that is translocated to a germ line alpha switch region. Mol Cell Biol. 1985 Mar;5(3):501–509. doi: 10.1128/mcb.5.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Showe L. C., Croce C. M. The role of chromosomal translocations in B- and T-cell neoplasia. Annu Rev Immunol. 1987;5:253–277. doi: 10.1146/annurev.iy.05.040187.001345. [DOI] [PubMed] [Google Scholar]
- Silva A. J., Johnson J. P., White R. L. Characterization of a highly polymorphic region 5' to JH in the human immunoglobulin heavy chain. Nucleic Acids Res. 1987 May 11;15(9):3845–3857. doi: 10.1093/nar/15.9.3845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. R. Chi hotspots of generalized recombination. Cell. 1983 Oct;34(3):709–710. doi: 10.1016/0092-8674(83)90525-1. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Ueda S., Obata M., Nikaido T., Nakai S., Honjo T. Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Cell. 1982 Jun;29(2):671–679. doi: 10.1016/0092-8674(82)90183-0. [DOI] [PubMed] [Google Scholar]
- Tsujimoto Y., Gorham J., Cossman J., Jaffe E., Croce C. M. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. doi: 10.1126/science.3929382. [DOI] [PubMed] [Google Scholar]
- Tsujimoto Y., Jaffe E., Cossman J., Gorham J., Nowell P. C., Croce C. M. Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11;14) chromosome translocation. Nature. 1985 May 23;315(6017):340–343. doi: 10.1038/315340a0. [DOI] [PubMed] [Google Scholar]
- Tutter A., Riblet R. Conservation of an immunoglobulin variable-region gene family indicates a specific, noncoding function. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7460–7464. doi: 10.1073/pnas.86.19.7460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller P., Jeffreys A. J., Wilson V., Blanchetot A. Organization of the human myoglobin gene. EMBO J. 1984 Feb;3(2):439–446. doi: 10.1002/j.1460-2075.1984.tb01825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wetton J. H., Carter R. E., Parkin D. T., Walters D. Demographic study of a wild house sparrow population by DNA fingerprinting. Nature. 1987 May 14;327(6118):147–149. doi: 10.1038/327147a0. [DOI] [PubMed] [Google Scholar]
- Wiggs J., Nordenskjöld M., Yandell D., Rapaport J., Grondin V., Janson M., Werelius B., Petersen R., Craft A., Riedel K. Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene. N Engl J Med. 1988 Jan 21;318(3):151–157. doi: 10.1056/NEJM198801213180305. [DOI] [PubMed] [Google Scholar]
- Wiman K. G., Clarkson B., Hayday A. C., Saito H., Tonegawa S., Hayward W. S. Activation of a translocated c-myc gene: role of structural alterations in the upstream region. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6798–6802. doi: 10.1073/pnas.81.21.6798. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yancopoulos G. D., Alt F. W. Regulation of the assembly and expression of variable-region genes. Annu Rev Immunol. 1986;4:339–368. doi: 10.1146/annurev.iy.04.040186.002011. [DOI] [PubMed] [Google Scholar]