On 4 September at 11:15 Kärt Ukkivi will defend her doctoral thesis in genetics “Mutagenic effect of transcription and transcription-coupled repair factors in Pseudomonas putida“.
Supervisor: Professor Maia Kivisaar, the Institute of Molecular and Cell Biology.
Opponent: Professor Elzbieta Kraszewska, Institute of Biochemistry and Biophysics, Warsaw (Poland).
For most of their lives in nature bacteria are nutrient-deprived and stressed due to ever-changing environmental conditions. To survive, microbial populations can rapidly evolve through formation of mutations. As mutations enable the bacteria to develop resistance to antibiotics and acquire protection to hosts immune response, it is necessary to understand the mechanisms that promote mutagenic processes.
It has been proposed that the essential process of RNA synthesis, i.e. transcription, is also a factor promoting formation of mutations. However, the exact mechanism and role of transcription in mutagenic processes is still unknown. In addition, it is unclear how the DNA repair coupled with transcription affects the occurrence of mutations. In bacteria transcription-coupled repair is mediated by repair proteins Mfd and UvrD. While transcription-coupled repair removes DNA lesions and should thereby maintain the genome integrity, accumulating body of evidence suggesting that in some circumstances transcription-coupled repair may instead induce the occurrence of mutations through the Mfd-dependent pathway.
In this thesis the role of transcription and transcription-coupled repair factors Mfd and UvrD in mutational processes was studied in soil bacterium Pseudomonas putida. This bacterium is a member of a large Pseudomonas genus, which comprises a diverse group of bacteria that are metabolically diverse and have a broad potential for adaptation to changing environmental conditions. Several members are also of great interest because of their prospects in biotechnological applications or their ability to cause disease in plants and animals.
Results of the thesis demonstrate that transcription is an endogenous process that promotes occurrence of genetic changes in P. putida - elevated transcription of the mutational target gene results in elevated mutation frequency. Repair coupled with transcription also has a role in the mutagenic processes - UvrD is essential for preventing occurrence of mutations, while Mfd promotes the occurrence of mutations in some conditions and may thus contribute to the evolution of bacteria.