ERC Starting Grant · 2024
Sifting through the 3D Genome: Computational Models of Homology Search in DNA Repair
Homology-directed repair is an essential, evolutionary conserved DNA repair pathway that accurately restores genetic information lost due to double-stranded breaks. Its key step is the ‘homology search’, where the broken DNA end locates its matching sequence, typically located on a sister chromatid, to use as a repair template. Despite its significance, the biophysical mechanism of this search within the complex environment of vertebrate genomes remains debated. Emerging hypotheses propose that this search is driven by ‘nucleoprotein’ filaments comprised of repair proteins bound to the broken DNA ends, that actively traverse the nuclear space to find and recognize homologous sequences. We…
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