One of the aims of bottom-up synthetic biology is the construction of rationally engineered cells that will act as chassis for particular biotechnological applications. This has the potential to increase predictability for design and modelling, and provide a more streamlined metabolism. Important questions are whether we can engineer cells to be more robust to evolution or whether we can design cells that have high mutation rates for directed evolution or safety considerations. We will elucidate the principles for the rational engineering of the DNA damage response (DDR), which is the collection of mechanisms that maintain the integrity of the genome.
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