title: Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity.
abstract: Although the nuclear processes responsible for genomic DNA replication and repair are well characterized, the pathways involved in mitochondrial DNA (mtDNA) replication and repair remain unclear. DNA repair has been identified as being particularly important within the mitochondrial compartment due to the organelle's high propensity to accumulate oxidative DNA damage. It has been postulated that continual accumulation of mtDNA damage and subsequent mutagenesis may function in cellular aging. Mitochondrial base excision repair (mtBER) plays a major role in combating mtDNA oxidative damage; however, the proteins involved in mtBER have yet to be fully characterized. It has been established that during nuclear long-patch (LP) BER, FEN1 is responsible for cleavage of 5' flap structures generated during DNA synthesis. Furthermore, removal of 5' flaps has been observed in mitochondrial extracts of mammalian cell lines; yet, the mitochondrial localization of FEN1 has not been clearly demonstrated. In this study, we analyzed the effects of deleting the yeast FEN1 homolog, RAD27, on mtDNA stability in Saccharomyces cerevisiae. Our findings demonstrate that Rad27p/FEN1 is localized in the mitochondrial compartment of both yeast and mice and that Rad27p has a significant role in maintaining mtDNA integrity.
authors.affiliation: Department of Biology, University of Rochester, NY 14627, United States.
authors.forename: Lidza
authors.initials: L
authors.lastname: Kalifa
authors.forename: Gisela
authors.initials: G
authors.lastname: Beutner
authors.forename: Naina
authors.initials: N
authors.lastname: Phadnis
authors.forename: Shey-Shing
authors.initials: SS
authors.lastname: Sheu
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Sia
mesh_terms: D000818:Animals; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D045585:Flap Endonucleases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D029701:Saccharomyces cerevisiae Proteins; D045585:Flap Endonucleases; C468323:RAD27 protein, S cerevisiae
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