‘Life by a Thousand Cuts’: DNA breaks drive mutagenesis in the human germline

Meiotic recombination commences with hundreds of programmed DNA breaks, however the degree to which they are accurately repaired remains poorly understood. We report that meiotic recombination is 8-fold more mutagenic for single-base substitutions than was previously understood, leading to de novo mutation in 1 in 4 human sperm and 1 in 12 human eggs. Its impact on indels and structural variants is even higher, with 100-1400-fold increases in rates per break. We uncover novel mutational signatures and footprints relative to break sites, which implicate error-prone mechanisms including translesion synthesis and end-joining repair pathways in meiotic break repair. These mechanisms drive mutagenesis in human germlines and lead to disruption of hundreds of genes genome-wide.

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As a reminder, the (gen)omics seminar series runs every other Thursday morning and is intended to increase interaction between individuals working in genomics across Oxford. We encourage in-person attendance where possible. There is time for discussion over tea, coffee and pastries after the talks.

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Please note, these meetings are closed meetings and only open to members of the University of Oxford to encourage sharing of new and unpublished data. Please respect our speakers and do not share the link with anyone outside of the university.
The aim of these seminars is to increase interaction between people working in Genomics across the University so we encourage in person attendance wherever possible.
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