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Spatial controls of homology search

Aurele Piazza and Angela Taddei (2026)

Current Opinion in Genetics and Development, 98:102450.

Homologous recombination is a conserved DNA double-strand break (DSB) repair pathway that uses an intact dsDNA molecule as a template. A filament of the RecA/Rad51 protein family catalyzes the search for this homologous template, in a process that minimally requires the collision of these two partners in the nuclear space. Orthogonal methodological developments recently revealed that this search for homology is a choreographed process under control by both 3D chromatin organizers of the structural maintenance of chromosomes (SMC) family and the structure and dynamics of the RecA/Rad51 filament. Here we review these advances that establish a novel framework for homology search, highlight the commonalities and distinctions between search facilitation strategies in eukaryotes and bacteria, and discuss outstanding open questions.
3D genome, genomic instability, Rad51, genome organization, DNA recombination