DNA damage induced bacterial filaments recover via asymmetric chromosome segregation and cell division
DNA damage induced bacterial filaments recover via asymmetric chromosome segregation and cell division
ISMATH
SADHIR
(JRF)
I work on understanding the regulation of error-prone DNA polymerases in bacteria
ADApting to DNA damage:
A conserved non-electrostatic switch mechanism drives a bacterial adaptive response to methylation damage
DNA methylation plays central roles in regulating essential processes, from enabling correction of replicative errors to controlling cell cycle. However, some methylation lesions can also be disruptive. Such methylation damage elicits two distinct responses in bacteria. The generalized damage response (SOS) is activated under most forms of DNA damage and can result in mutagenesis. The adaptive response, on the other hand, is non-mutagenic and specific only to methylation damage. While the SOS response is ubiquitously present, conservation and relevance of the adaptive response beyond the well-studied E. coli model remains less appreciated. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), that regulates a methylation-inducible adaptive response in Caulobacter. This response is activated independent of the SOS response, regulates expression of genes involved in direct repair, and is essential for survival under methylation damage. Molecular characterization of Cada2 reveals a novel domain organization and DNA binding region that is distinct from its E. coli counterpart (Ada), and conserved in all bacteria encoding a Cada2-like homolog instead. Interestingly, regardless of mechanistic differences, key dynamics of the response itself remain conserved between the two organisms. We further find that the central regulator of the adaptive response appears to undergo domain shuffling across the bacterial kingdom; although highly conserved, it has several distinct domain architectures in bacterial genomes. Thus, despite diverse organizations and mechanisms of regulation, widespread occurrence of adaptive response regulators such as Ada (E. coli-like) and Cada2 (Caulobacter-like) underscores the importance of a methylation-specific bacterial DNA damage response. We are now excited to understand what selection pressures have driven the evolution and conservation of a dedicated response to methylation damage in bacteria.