title: Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.
abstract: To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the mammalian mitochondria. We demonstrate localization of REV3 in the mitochondria of mammalian tissue as well as cell lines. REV3 associates with POLG and mitochondrial DNA and protects the mitochondrial genome from DNA damage. Inactivation of Rev3 leads to reduced mitochondrial membrane potential, reduced OXPHOS activity, and increased glucose consumption. Conversely, inhibition of the OXPHOS increases expression of Rev3. Rev3 expression is increased in human primary breast tumors and breast cancer cell lines. Inactivation of Rev3 decreases cell migration and invasion, and localization of Rev3 in mitochondria increases survival and the invasive potential of cancer cells. Taken together, we demonstrate that REV3 functions in mammalian mitochondria and that mitochondrial REV3 is associated with the tumorigenic potential of cells.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Bhupendra
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Kjerstin M
authors.initials: KM
authors.lastname: Owens
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Ayyasamy
authors.initials: A
authors.lastname: Vanniarajan
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharine's, Ontario, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.affiliation: Departments of Genetics, Pathology, Environmental Health, Center for Free Radical Biology, Center for Aging and UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, United States of America.
authors.forename: Keshav K
authors.initials: KK
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D019610:Cytoprotection; D004249:DNA Damage; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D054629:Genome, Mitochondrial; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010085:Oxidative Phosphorylation; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C118285:REV3L protein, human