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DNA replication and recombination are common to all cells. Errors in these processes lead to many diseases in humans, including cancer, and many fundamental questions are still unresolved. Due to recent technical advances in microscopy and other techniques, these dynamic processes can now be studied in time and space in both prokaryotes and eukaryotes. Moreover, breakthroughs in the biochemical reconstitution of processes in DNA replication and recombination repair as well as single particle electron microscopy promise to reveal new mechanisms at near-atomic resolution; and new DNA sequencing technologies make it possible to study these key processes in great details. Mechanistic similarities across the three domains of life provide new basic principles while differences identify potential targets for therapeutic intervention.