Meiotic DNA breaks drive multifaceted mutagenesis in the human germline
Post seminar tea, coffee and biscuits will be available in the Combination Room.
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.
Date: 22 September 2023, 14:00 (Friday, -2nd week, Michaelmas 2023)
Venue: Sir William Dunn School of Pathology, South Parks Road OX1 3RE
Venue Details: EPA Seminar Room
Speaker: Dr Anjali Hinch (University of Oxford)
Organising department: Sir William Dunn School of Pathology
Organiser: Jo Peel (University of Oxford, Sir William Dunn School of Pathology)
Host: Professor Matthew Freeman (Sir William Dunn School of Pathology, University of Oxford)
Part of: Dunn School of Pathology Departmental Seminars
Booking required?: Not required
Audience: Members of the University only
Editor: Jo Peel