학술논문
Kromosomski rearanžmani u ozračenim mrtvim stanicama bakterije Deinococcus radiodurans: uloga insercijskih sekvenci i proteina RecA
Radiation-induced chromosomal rearrangements in dead Deinococcus radiodurans cells: the role of insertion sequences and RecA protein
Radiation-induced chromosomal rearrangements in dead Deinococcus radiodurans cells: the role of insertion sequences and RecA protein
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Croatian
Abstract
U ovom radu istraživani su fundamentalni uzroci stanične smrti u robusnoj bakteriji Deinococcus radiodurans koja preživljava izlaganje ekstremnom isušivanju, ionizirajućem zračenju ili mutagenim kemijskim spojevima. Rezultati ovog istraživanja pokazali su da je ključna „meta“ stanične smrti funkcija (proteom), a ne informacija (genom). Analizirana je sudbina oštećene DNA (dvolančani lomovi i kromosomski rearanžmani u preživjelim i mrtvim stanicama) i oksidacijom oštećenih (karboniliranih) proteina u trenutku "odluke" o preživljenju ili smrti stanice; pronađena je korelacija između stanične smrti i zračenjem izazvane karbonilacije proteina, ali ne i oštećenja molekule DNA. Stanična smrt je inicirana progresivnim gubitkom vitalnih funkcija, uključujući popravak DNA, koji nastaje uslijed povećanja razine ireverzibilnih oštećenja proteina. Dok se popravak DNA odvija slično u ugibajućim i preživjelim stanicama, nepovratna točka smrti je depolarizacija i permeabilnost stanične membrane koja je potaknuta oksidacijom novosintetiziranih membranskih proteina, što u konačnici rezultira fatalnim „otpuštanjem“ staničnih metabolita i iona potrebnih za sve biosintetske procese. Ova fatalna promjena stanične membrane je aktivan proces budući da ovisi o transkripciji i translaciji de novo u letalno ozračenim stanicama bakterije D. radiodurans.
This research was focused on the fundamental cause(s) of cell death in a robust bacterium, Deinococcus radiodurans, known to survive extreme exposures to desiccation, radiation or mutagenic chemicals. The results of this study proved that the key target in cell death is function (proteome) rather than information (genome). Analyzing the fate of the damaged DNA (double-strand breaks and chromosomal rearrangements in surviving and dead cells) and oxydatively damaged (carbonylated) proteins when the “decision“ between survival and death takes place, cell death showed correlation with radiation-induced proteome carbonylation but not with DNA breakage. Cell death is initiated by the progressive loss of vital functions, including DNA repair, caused by increasing levels of the irreversible protein damage. While DNA repair proceeds similarly in dying and surviving cells, the deadly point of no-return is membrane depolarization and permeability - triggered by neo-synthesized oxidized membrane proteins - causing the fatal leakage of metabolites and ions required for all biosynthetic processes. This fatal change in cell membrane is an active process since it depends on de novo transcription and translation in lethally irradiated D. radiodurans cells.
This research was focused on the fundamental cause(s) of cell death in a robust bacterium, Deinococcus radiodurans, known to survive extreme exposures to desiccation, radiation or mutagenic chemicals. The results of this study proved that the key target in cell death is function (proteome) rather than information (genome). Analyzing the fate of the damaged DNA (double-strand breaks and chromosomal rearrangements in surviving and dead cells) and oxydatively damaged (carbonylated) proteins when the “decision“ between survival and death takes place, cell death showed correlation with radiation-induced proteome carbonylation but not with DNA breakage. Cell death is initiated by the progressive loss of vital functions, including DNA repair, caused by increasing levels of the irreversible protein damage. While DNA repair proceeds similarly in dying and surviving cells, the deadly point of no-return is membrane depolarization and permeability - triggered by neo-synthesized oxidized membrane proteins - causing the fatal leakage of metabolites and ions required for all biosynthetic processes. This fatal change in cell membrane is an active process since it depends on de novo transcription and translation in lethally irradiated D. radiodurans cells.