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Frequent chromosomal translocations induced by DNA double-strand breaks

Author

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  • Christine Richardson

    (Cell Biology Program, Memorial Sloan-Kettering Cancer Centre and Cornell University Graduate School of Medical Sciences)

  • Maria Jasin

    (Cell Biology Program, Memorial Sloan-Kettering Cancer Centre and Cornell University Graduate School of Medical Sciences)

Abstract

The faithful repair of DNA damage such as chromosomal double-strand breaks (DSBs) is crucial for genomic integrity. Aberrant repair of these lesions can result in chromosomal rearrangements, including translocations, which are associated with numerous tumours1,2. Models predict that some translocations arise from DSB-induced recombination in differentiating lymphoid cell types3,4,5 or from aberrant repair of DNA damage induced by irradiation or other agents6,7,8; however, a genetic system to study the aetiology of these events has been lacking. Here we use a mouse embryonic stem cell system to examine the role of DNA damage on the formation of translocations. We find that two DSBs, each on different chromosomes, are sufficient to promote frequent reciprocal translocations. The results are in striking contrast with interchromosomal repair of a single DSB in an analogous system in which translocations are not recovered. Thus, while interchromosomal DNA repair does not result in genome instability per se, the presence of two DSBs in a single cell can alter the spectrum of repair products that are recovered.

Suggested Citation

  • Christine Richardson & Maria Jasin, 2000. "Frequent chromosomal translocations induced by DNA double-strand breaks," Nature, Nature, vol. 405(6787), pages 697-700, June.
    • Handle: RePEc:nat:nature:v:405:y:2000:i:6787:d:10.1038_35015097
    DOI: 10.1038/35015097
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    Cited by:

    1. Li Cheng & Shijun Zhao & Tianyi Li & Sha Hou & Zhouqing Luo & Jinsheng Xu & Wenfei Yu & Shuangying Jiang & Marco Monti & Daniel Schindler & Weimin Zhang & Chunhui Hou & Yingxin Ma & Yizhi Cai & Jef D., 2024. "Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Aldo S. Bader & Martin Bushell, 2023. "iMUT-seq: high-resolution DSB-induced mutation profiling reveals prevalent homologous-recombination dependent mutagenesis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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