Mutagenic potential of DNA damage repair and tolerance mechanisms under starvation stress

Abstract

Upon being confronted with DNA damage, bacteria, as any other cell, have two options for survival: either to repair the DNA or to tolerate the damage. If neither of the two succeeds and the lesions remain in the DNA, the cell dies. There are several partially redundant repair pathways to cope with damage, as well as several specialized DNA polymerases to carry out replication across lesions in DNA. In general, DNA repair and damage tolerance due to the action of specialized DNA polymerases are temporally separated processes. First, repair of damage, an intrinsically error-free process is initiated. If damage is not repaired within a certain time, the specialized, often error-prone DNA polymerases are allowed to save the cell from the worst. The best and probably most studied example of these ‘sequential’ repair and tolerance is the way bacteria deal with UV-induced DNA damage. I have here addressed the influence of mechanisms of DNA repair and tolerance on mutational processes in bacteria under conditions of carbon starvation. The energy status of bacteria in these conditions is low and chromosome replication and bacterial division are strongly reduced. I have investigated Pseudomonas putida pathways that deal with UV-induced damage: nucleotide excision repair and the activity of specialized DNA polymerases.Looduses elavad bakterid pidevalt muutuvates keskkonnatingimustes, kus nende kasv on pärsitud toitainete vähesuse tõttu ning bakterite vahel toimub pidev konkurents olemasolevate toitainete pärast. Sellistes tingimustes toimub bakterite kohastumine muutlike keskkonna oludega. Lisaks füsioloogilistele ümberkorraldustele toimub bakteritel ka geneetiline kohastumine: tõuseb mutatsioonide tekkesagedus, mis võimaldab suurendada populatsiooni geneetilist mitmekesisust. Mutatsioonsagedust suurendavad ka mitmete eksogeensete ja endogeensete tegurite toimel tekkinud DNA kahjustused. Rakkudes on DNA kahjustuste eemaldamiseks mitmeid mehhanisme. Lisaks DNA kahjustuste parandamisele on rakkudes ka mehhanismid, mis võimaldavad DNA kahjustuste parandamist edasi lükata ehk kahjustusi taluda. Oma töös olen uurinud, kuidas mõjutavad mehhanismid, mille peamiseks funktsiooniks on raku kaitsmine UV-kiirguse mõjul tekkinud DNA kahjustuste eest, mutatsiooniprotsesse nälgivates bakterirakkudes.