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Crossing boundaries:
Regulating DNA polymerases in diverse growth phases

Although at the population-level our work, and that of others, underscores specificity in DNA damage responses and repair pathway action, these boundaries can be crossed in certain growth conditions to augment cellular survival under stress. We uncovered one such beneficial cross-talk between error-prone translesion synthesis (TLS) and error-free NER in non-replicating cells. While current models suggest that TLS is predominantly associated with ongoing replication, we used live-cell imaging to show that TLS is functional and relevant even in the absence of replication. This action required lesion processing by NER. We found that such repair promoted survival of non-replicating cells when released into replication-conducive conditions, suggesting that cross-talk may be an important mechanism by which these cells survive DNA damage and potentially increase chances for mutagenesis. This work inspired us to study replication regulation in diverse growth conditions. In nature, bacteria occupy diverse ecological niches and can face stresses such as starvation, antibiotic exposure and competition. In these conditions, cells need to modulate cell cycle progression and growth rates. For example, in stationary phase of growth, bacteria are reported shut down basic cellular processes including replication. We are interested in understanding how DNA polymerase activity is regulated and how mutagenic processes are modulated as cells transition into this nutrient-limiting phase of growth.

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