DOI: 10.1073/pnas.94.22.12018. Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends

Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends

10.1073/pnas.94.22.12018

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Chromosomal translocations induced by ionizing radiation and radiomimetic drugs are thought to arise by incorrect joining of DNA double-strand breaks. To dissect such misrepair events at a molecular level, large-scale, bleomycin-induced rearrangements in the aprt gene of Chinese hamster ovary D422 cells were mapped, the breakpoints were sequenced, and the original non- aprt parental sequences involved in each rearrangement were recovered from nonmutant cells. Of seven rearrangements characterized, six were reciprocal exchanges between aprt and unrelated sequences. Consistent with a mechanism involving joining of exchanged double-strand break ends, there was, in most cases, no homology between the two parental sequences, no overlap in sequences retained at the two newly formed junctions, and little or no loss of parental sequences (usually ≤2 bp) at the breakpoints. The breakpoints were strongly correlated ( P < 0.0001) with expected sites of bleomycin-induced, double-strand breaks. Fluorescence in situ hybridization indicated that, in six of the mutants, the rearrangement was accompanied by a chromosomal translocation at the aprt locus, because upstream and downstream flanking sequences were detected on separate chromosomes. The results suggest that repair of free radical-mediated, double-strand breaks in confluence-arrested cells is effected by a conservative, homology-independent, end-joining pathway that does not involve single-strand intermediate and that misjoining of exchanged ends by this pathway can directly result in chromosomal translocations.

Bibliography

Wang, P., Zhou, R.-H., Zou, Y., Jackson-Cook, C. K., & Povirk, L. F. (1997). Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends. Proceedings of the National Academy of Sciences, 94(22), 12018â12023.

Authors 5

Peng Wang (first)
Rui-Hua Zhou (additional)
Ying Zou (additional)
Colleen K. Jackson-Cook (additional)
Lawrence F. Povirk (additional)

References 35 Referenced 28

D E Lea Actions of Radiations on Living Cells (Cambridge Univ. Press, Cambridge, MA, 1946). / Actions of Radiations on Living Cells by Lea D E (1946)
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P Pfeiffer, S Thode, J Hancke, W Vielmetter Mol Cell Biol 14, 888–895 (1994). / Mol Cell Biol by Pfeiffer P (1994)
M Meuth Mobile DNA, eds D Berg, M Howe (Am. Soc. Microbiol., Washington, DC), pp. 833–853 (1989). / Mobile DNA by Meuth M (1989)
D B Roth, J H Wilson Genetic Recombination, eds R Kucherlapati, G R Smith (Am. Soc. Microbiol., Washington, DC), pp. 621–653 (1988). / Genetic Recombination by Roth D B (1988)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 2 months ago (June 6, 2022, 5:31 p.m.)
Indexed	1 month, 2 weeks ago (July 12, 2025, 6:58 p.m.)
Issued	27 years, 10 months ago (Oct. 28, 1997)
Published	27 years, 10 months ago (Oct. 28, 1997)
Published Online	27 years, 10 months ago (Oct. 28, 1997)
Published Print	27 years, 10 months ago (Oct. 28, 1997)

Funders 0

None

BibTeX

@article{Wang_1997, title={Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.22.12018}, DOI={10.1073/pnas.94.22.12018}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Wang, Peng and Zhou, Rui-Hua and Zou, Ying and Jackson-Cook, Colleen K. and Povirk, Lawrence F.}, year={1997}, month=oct, pages={12018–12023} }

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