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- W3213706593 abstract "Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here, we uncover a distinct type of mutational event in which deletions form via joining of ends from two closely spaced DSBs (double cuts) within a single hotspot or at adjacent hotspots on the same or different chromatids. Deletions occur in normal meiosis but are much more frequent when DSB formation is dysregulated in the absence of the ATM kinase. Events between chromosome homologs point to multi-chromatid damage and aborted gap repair. Some deletions contain DNA from other hotspots, indicating that double cutting at distant sites creates substrates for insertional mutagenesis. End joining at double cuts can also yield tandem duplications or extrachromosomal circles. Our findings highlight the importance of DSB regulation and reveal a previously hidden potential for meiotic mutagenesis that is likely to affect human health and genome evolution." @default.
- W3213706593 created "2021-11-22" @default.
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- W3213706593 date "2021-11-01" @default.
- W3213706593 modified "2023-10-11" @default.
- W3213706593 title "De novo deletions and duplications at recombination hotspots in mouse germlines" @default.
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- W3213706593 doi "https://doi.org/10.1016/j.cell.2021.10.025" @default.
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