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Central to life is the propagation of genetic material. Cells constantly face the threat of DNA damage. Incorrectly repaired or unrepaired damage can lead to mutations, loss of genetic information, or even cell death. Thus, cells must ensure faithful duplication and segregation of DNA across generations. The importance of this process is highlighted by the presence of checkpoints to regulate cell cycle progression and cell division, coupled to surveillance for genome maintenance. Checkpoints for genome integrity are universally conserved across domains of life, as are the mechanisms for repair and error correction. However, although repair is essential for genome maintenance, some pathways are also sources of mutagenesis. Hence, repair pathway choice is regulated to (i) ensure that the appropriate pathway is employed during repair, and (ii) control activity of error-free and error-prone
systems to ensure balance between genome integrity maintenance and rates of stress-induced mutagenesis. This becomes particularly relevant in microbial systems that live in constantly fluctuating environments, where modulation of these pathways can have a significant impact on cellular adaptation and survival under stress. While DNA damage responses and repair pathways have been well-studied in isolated contexts in vitro, their dynamics, mechanisms of action, and regulation in a living cell are still active areas of exploration. In our lab we study how genome maintenance mechanisms are coordinated and regulated in vivo in microbes. For this, we employ quantitative live-cell imaging techniques to follow repair in real-time, in conjunction with genetic and molecular tools to introduce specific perturbations. In this talk, I will share some of our recent efforts to understand
how specific steps of DNA damage response and repair are regulated in microbial systems.
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