NIH R01 · 2025
Pre-synaptic events in homologous recombination and maintenance of genomic stability
SUMMARY Lesions, breaks, and errors in DNA are drivers of genomic instability. Double-stranded DNA breaks (DSBs) are a particularly severe form of damage and are repaired by the homologous recombination (HR) pathway. On average, ~10 to 50 DSBs occur per cell per day and thus pose the highest risk to genomic integrity. Unrepaired DSBs lead to gross chromosomal rearrangements and are key drivers of cancers. HR is initiated when the DSB is resected to generate ssDNA. Rad51 is the recombinase that drives HR and forms a helical nucleoprotein filament on the resected ssDNA. This step, termed ‘pre-synaptic nucleoprotein filament formation’ commits to repairing the DSB through the HR pathway. Not…
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