Replication and Recombination of mitochondrial DNA in Yeast
Kuupäev
2010-11-16
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Ajakirja pealkiri
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Abstrakt
Mitokondrid on kõrgemate organismide nagu loomade, taimede ja seente rakkudes olevad väikesed organellid. Mitokondrid on esmatähtsad ainevahetusel ja üks nende peamisi ülesandeid on energia tootmine. Selleks on mitokondritel vaja mitmeid valke, mis on koondunud membraaniga seotud kompleksidesse. Enamus nendest valkudest on kodeeritud tuuma kromosoomide poolt, kuid mõned hädavajalikud subühikud mitokondri DNA poolt. Mitokondrid peavad seega oma väikest genoomi hästi säilitama, et vigadeta DNA-d saaks transkribeerida ja funktsionaalseid valke toota, näiteks energia saamiseks.
Kaua aega usuti, et kõikide eukarüootsete rakkude mitokondrite DNA näeb samasugune välja ning seda paljundatakse ja säilitatakse sarnaselt nii loomades, taimedes kui seentes. Pärmseeni, mille uurimiseks on olemas head geneetilise vahendid, kasutatakse seepärast eukarüootide mudelina.
Selles väitekirjas kirjeldatud analüüsid tõestavad, et kuigi loomade ja pärmide mitokondriaalse DNA (mtDNA) säilitamises on sarnasusi, on seal ka olulisi erinevusi, mida ei ole siiani selgelt välja toodud. Näiteks on loomade mtDNA ringikujuline, pärmide mtDNA aga lineaarne ja harunenud. Loomade DNA süntees algab spetsiaalse RNA-praimeri sünteesiga kindlas DNA punktis. Pärmides paarduvad ja rekombineeruvad homoloogsed DNA järjestused omavahel, mille käigus üks homoloogne DNA invaseerub teise struktuuri. See invasioon tekitab DNA sünteesi alguspunkti, mis funktsionaalselt vastab loomade RNA-praimerile. Need erinevad DNA säilitamise süsteemid vajavad spetsiifilisi valke. Viimastel aastatel on näidatud, et pärmide ja loomade mitokondrites on palju sarnaseid, aga ka mitmeid erinevaid valke. Need leiud ja käesoleva väitekirja tulemused on olulised ka väljaspool baasteadust. Käesolevas uurimuses kasutati mudelorganismina pärmi Candida albicans. Erinevalt enam uuritud pagaripärmist Saccharomyces cerevisiae põhjustab C. albicans naha ja limaskestade nakkusi. Nõrgestunud immuunsüsteemiga patsientidele (nt. vähi ja AIDSi haigetele) võivad need nakkused olla eluohtlikud. Käesoleva töö tulemused võivad aidata leida ravimeid, mis tõrjuvad seenhaigusi, samas inimesele vähe või üldse mitte kahju tegemata.
Mitochondria are small separate organelles within cells of higher organisms such as animals, plants or fungi. They are of major importance for the metabolism, and one of their main functions is the production of energy. In order to produce energy, mitochondria need a number of proteins which are grouped to membrane associated complexes to carry out the energy production. Many of these proteins are encoded by genes of the main chromosomes in the nucleus, but a few essential subunits are encoded on DNA within the mitochondria. Mitochondria therefore need to maintain their own small genome with great care to guarantee error-free DNA, that is transcribed and translated in order to deliver functional proteins products e.g. for energy production. It has been a longstanding belief, that mitochondria in different eukaryotic cells carry an equally looking DNA which is reproduced and maintained in the same ways in animals, plants and fungi. Therefore, yeast-fungi are widely used as eukaryotic model organisms because of the availability of genetics tools. The investigations conducted in the course of this thesis show, that although there are indeed similarities between animal and yeast mitochondrial DNA (mtDNA) maintenance, there are also important differences that have not been clearly shown until now. For example, while the mtDNA in animals appears in form of a circular molecule, yeast mitochondria contain linear and branched ones. In animals the DNA reproduction is started by making a specific starter molecule, termed RNA-primer, at a certain point on the DNA. In yeast, homologous DNA sequences are paired and recombined, in the course of which one homologous DNA invades the other. This invasion provides a starting point for DNA synthesis analogous to the RNA-primer that is used in mammals. These differing maintenance systems require specific protein machineries. In recent years it was shown that mitochondria in yeast and animals contain many similar but also a number of differing proteins. Such findings and also the results of this thesis have implications beyond the general use of basic research. The yeast model organism used in experiments of the current work was Candida albicans. Other than the commonly known baker´s yeast Saccharomyces cerevisiae, the potential pathogen C. albicans causes skin and mucosal infections. These can be life threatening for patients whose immune system is compromised (e.g. through cancer or AIDS). Findings like the ones in this thesis open ways to find unique targets for drugs that may specifically attack the pathogen without or little side effects for a patient.
Mitochondria are small separate organelles within cells of higher organisms such as animals, plants or fungi. They are of major importance for the metabolism, and one of their main functions is the production of energy. In order to produce energy, mitochondria need a number of proteins which are grouped to membrane associated complexes to carry out the energy production. Many of these proteins are encoded by genes of the main chromosomes in the nucleus, but a few essential subunits are encoded on DNA within the mitochondria. Mitochondria therefore need to maintain their own small genome with great care to guarantee error-free DNA, that is transcribed and translated in order to deliver functional proteins products e.g. for energy production. It has been a longstanding belief, that mitochondria in different eukaryotic cells carry an equally looking DNA which is reproduced and maintained in the same ways in animals, plants and fungi. Therefore, yeast-fungi are widely used as eukaryotic model organisms because of the availability of genetics tools. The investigations conducted in the course of this thesis show, that although there are indeed similarities between animal and yeast mitochondrial DNA (mtDNA) maintenance, there are also important differences that have not been clearly shown until now. For example, while the mtDNA in animals appears in form of a circular molecule, yeast mitochondria contain linear and branched ones. In animals the DNA reproduction is started by making a specific starter molecule, termed RNA-primer, at a certain point on the DNA. In yeast, homologous DNA sequences are paired and recombined, in the course of which one homologous DNA invades the other. This invasion provides a starting point for DNA synthesis analogous to the RNA-primer that is used in mammals. These differing maintenance systems require specific protein machineries. In recent years it was shown that mitochondria in yeast and animals contain many similar but also a number of differing proteins. Such findings and also the results of this thesis have implications beyond the general use of basic research. The yeast model organism used in experiments of the current work was Candida albicans. Other than the commonly known baker´s yeast Saccharomyces cerevisiae, the potential pathogen C. albicans causes skin and mucosal infections. These can be life threatening for patients whose immune system is compromised (e.g. through cancer or AIDS). Findings like the ones in this thesis open ways to find unique targets for drugs that may specifically attack the pathogen without or little side effects for a patient.
Kirjeldus
Väitekirja elektrooniline versioon ei sisalda publikatsioone.
Märksõnad
dissertatsioonid, bioloogia, mitokondrid, pärm, DNA