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Evolutionary loss of 8-oxo-G repair components among eukaryotes.doc

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Evolutionary loss of 8-oxo-G repair components among eukaryotes

Janssonetal.GenomeIntegrity2010,1:12 /content/1/1/12 GENOME INTEGRITY RESEARCH OpenAccess Evolutionarylossof8-oxo-Grepaircomponents amongeukaryotes KristinaJansson,AndersBlomberg,PerSunnerhagen,MagnusAlmRosenblad* Abstract Background:WehaveexaminedthephylogeneticpatternamongeukaryotesofhomologuesoftheE.coli7,8- dihydro-8-oxoguanine(8-oxo-G)repairenzymesMutY,MutM,andMutT. Results:TheseDNArepairenzymesarepresentinalllargephylogeneticgroups,withMutMhomologuesbeing themostuniversallyconserved.Allchordatesandechinodermswerefoundtopossessallthree8-oxo-Grepair components.Likewise,theredandgreenalgaeexaminedhaveallthreerepairenzymes,whileallland-livingplants haveMutYandMutMhomologues,butlackMutT.However,forsomephyla,tostomes,amorepatchy distributionwasfound.Nematodesprovideastrikingexample,whereCaenorhabditisistheonlyidentifiedexample ofanorganismgrouphavingnoneofthethreerepairenzymes,whilethegenomeofanothernematode, Trichinellaspiralis,insteadencodesallthree.Themostcomplexdistributionexistsinfungi,wheremanydifferent patternsofretentionorlossofthethreerepaircomponentsarefound.Inaddition,wefoundsequenceinsertions nearorwithinthecatalyticsitesofMutY,MutM,andMutTtobepresentinsomesubgroupsofAscomycetes. Conclusion:The8-oxo-Grepairenzymesareancientinorigin,andlossofindividual8-oxo-Grepaircomponentsat severaldistinctpointsinevolutionappearstobethemostlikelyexplanationforthephylogeneticpatternamong eukaryotes. Background oxo-G-specific BER enzymes MutY, MutM, and MutT To maintain structural integrity of DNA, organisms [3].MutTisan8-oxo-dGTPasethatpreventsincorpora- have developed DNA repair mechanisms. These have tion of 8-oxo-G into DNA [4]. MutM excises 8-oxo-G evolved both in complexity and specificity to ensure paired with C[5], while MutY is an adenine-DNA gly- genomic integrity against the constant threats from cosylase that excises A paired with 8-oxo-G [6]. The damagingagentsofendogenousandexogenousorigins. MutYandMutMglycosylasesarebothmembersofthe DamagetoDNAb