Tatjana Jatsenko „Role of translesion DNA polymerases in mutagenesis and DNA damage tolerance in Pseudomonads”

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View all other units

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Date:

21.09.2011 - 12:15

On 21 September at 12:15 Tatjana Jatsenko will defend her doctoral thesis „Role of translesion DNA polymerases in mutagenesis and DNA damage tolerance in Pseudomonads”.

Supervisor:
Professor Maia Kivisaar, Molecular and Cell Biology Institute, University of Tartu

Opponent:
Research Fellow Vincent Pagès, PhD,Cancer Research Center of Marseille (CRCM), France

Summary:
The integrity of our hereditary material is constantly challenged by both endogenous agents formed during normal cellular metabolism and by various exogenous factors, like UV-light and chemicals found everywhere in the environment. Damage in DNA can block genome replication, which can lead to genomic instability and death of the cell. To overcome these blocks, organisms have evolved DNA damage tolerance mechanisms that allow completion of DNA replication in the presence of damage. One of them is translesion DNA synthesis (TLS), which is mediated by specialized TLS DNA polymerases that are able replicate over the replication-blocking DNA damage. Information encoded by a damaged nucleotide is usually inaccurate, therefore TLS is inherently error-prone process. As such, TLS polymerases not only protect cells against DNA damage, but also represent a potential source of mutations – a material for evolution, but also a cause of disease in humans. In bacteria, genetic diversity generated by TLS polymerases is critical for the acquisition of antibiotic resistance. Therefore, a lot of research is now undertaken to use TLS polymerases as a target for cancer or antimicrobial treatment. In the present work, I describe the role of TLS polymerases in two representatives of Pseudomonas, important human pathogen Pseudomonas aeruginosa and soil bacterium Pseudomonas putida. These organisms possess three TLS polymerases: Pol II, Pol IV and ImuABC. The results of our work revealed that in P. putida TLS polymerases might leave mutagenic fingerprints in the genome during normal growth of bacteria, suggesting their potential role in bypass past endogenously formed DNA damage. Moreover, Pol II and Pol IV might be involved in DNA replication in the absence of replicative DNA polymerase I. Both Pol IV and ImuABC in Pseudomonads are involved in DNA alkylation damage tolerance. Replication across alkylation damage by ImuABC is highly mutagenic, Pol IV, on the contrary, performs very accurate bypass. One of the important findings of my study was that simple switch in growth temperature of bacteria changed the cell’s strategy to deal with alkylation DNA damage and role of TLS in it.

Location:

Tartu Ülikooli molekulaar- ja rakubioloogia instituudis (Riia 23-217, Tartu Ülikooli molekulaar- ja rakubioloogia instituudi auditoorium)

URL:

hdl.handle.net/10062/61278

Event category:

Defence

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Tatjana Jatsenko „Role of translesion DNA polymerases in mutagenesis and DNA damage tolerance in Pseudomonads”

February