Nuclear and mitochondrial DNA repair: similar pathways?
MitochondrionPublished 16 March 2005
Nicolai Balle Larsen, Merete Rasmussen, Lene Juel Rasmussen
Citations281
SJR quartileQ2
SJR score1.24
SNIP0.93
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TL;DR
Comparisons between nDNA and mtDNA repair pathways are made and a model for how these pathways interact in mitochondria is proposed.
Abstract
Mitochondrial DNA (mtDNA) alterations are implicated in a broad range of human diseases and alterations of the mitochondrial genome are assumed to be a result of its high susceptibility to oxidative damage and its limited DNA repair compared to nuclear DNA (nDNA). Characterization of DNA repair mechanisms has generally focused on these processes in nDNA but increasing interest and research effort have contributed to our knowledge of the mechanisms underlying DNA repair in mitochondria. In this review, we make comparisons between nDNA and mtDNA repair pathways and propose a model for how these pathways interact in mitochondria.
Keywords
Biochemistry, Genetics and Molecular Biology
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Recent studies indicate that the MMR genes may be involved in the pathogenesis of even a broader spectrum of tumors in one way or another, with the emphasis on their implications in cancer development.
Annual Review of BiochemistryEukaryotic DNA Polymerases
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Trends in Biochemical SciencesThe base excision repair pathway
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The base excision repair pathway has evolved to protect cells from the deleterious effects of endogenous DNA damage induced by hydrolysis, reactive oxygen species and other intracellular metabolites that modify DNA base structure.
Proceedings of the National Academy of SciencesThe Absence of a Pyrimidine Dimer Repair Mechanism in Mammalian Mitochondria
532 Citations1974David A. Clayton, Jackie N. Doda +1 more
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Annual Review of MicrobiologyDNA Mismatch Repair: Molecular Mechanisms and Biological Function
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Annual Review of BiochemistryDNA Polymerase γ, The Mitochondrial Replicase
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Molecular Biology of the CellExpression and Differential Intracellular Localization of Two Major Forms of Human 8-Oxoguanine DNA Glycosylase Encoded by Alternatively Spliced OGG1 mRNAs
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Angewandte Chemie International EditionChemistry and Biology of DNA Repair
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Free Radical Biology and MedicineRepair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells1,2 1Guest Editor: Miral Dizdaroglu 2This article is part of a series of reviews on “Oxidative DNA Damage and Repair.” The full list of papers may be found on the homepage of the journal.
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While nuclear BER decreases with age, the mitochondrial DNA repair may increase with age; however, this increase is not enough to prevent the gradual accumulation of lesions in the mitochondrialDNA with age.
BiochimieRepair of DNA double strand breaks by non-homologous end joining
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This review discusses how DNA-dependent protein kinase and other accessory proteins may function in the repair of DSBs produced by ionizing radiation (IR) and by V(D)J recombination.
GeneticsCharacterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions.
354 Citations1992Robert A. Reenan, Richard D. Kolodner
Results indicate that MSH1 plays a role in repair or stability of mtDNA and MSH2 plays a roles in repair of 4-bp insertion/deletion mispairs in the nucleus.
Genes & DevelopmentTranslesion DNA synthesis in eukaryotes: A one- or two-polymerase affair
338 Citations2002Satya Prakash, Louise Prakash
The important findings and major conclusions that have emerged regarding translesion DNA synthesis (TLS) in eukaryotes are highlighted.
Mutation research. Fundamental and molecular mechanisms of mutagenesisMitochondrial DNA repair and aging
336 Citations2002Bhaskar S. Mandavilli, Janine H. Santos +1 more
The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell.
PubMedRepair of 8-oxodeoxyguanosine lesions in mitochondrial dna depends on the oxoguanine dna glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial dna of OGG1-defective mice.
326 Citations2001Nadja C. de Souza‐Pinto, Lars Eide +6 more
It is demonstrated that the mitochondrial 8-oxodG DNA glycosylase/apurinic DNA lyase activity is the mitochondrial isoform of OGG1, and it is found that mtDNA isolated from liver from Ogg1-null mutant animals contained 20-fold more 8- oxodG than mtDNA from wild-type animals.
Mutation research. Fundamental and molecular mechanisms of mutagenesisPathways for mitotic homologous recombination in mammalian cells
310 Citations2003Thomas Helleday
The substrates for HR, the pathways of repair, and their end products (i.e. sister chromatid exchange (SCE), gene conversion, deletions or tandem duplications) are discussed.
Nucleic Acids ResearchNuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene
304 Citations1997Hilde Nilsen, Marit Otterlei +5 more
Coupled transcription/translation in rabbit reticulocyte lysates demonstrated that both proteins are catalytically active and the significance of the N-terminal sequences in UNG1 and UNG2 for subcellular targeting was studied.
Nucleic Acids ResearchIdentification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria
303 Citations2000Toshio Ohtsubo
An enzyme activity introducing an alkali-labile site at 2-hydroxyadenine (2-OH-A) in double-stranded oligonucleotides was detected in nuclear extracts of Jurkat cells and hMYH is likely to possess both adenine and 2- OH-A DNA glycosylase activities.
Nucleic Acids ResearchMitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage
280 Citations1998Masashi Takao, Hiroyuki Aburatani +2 more
The results suggest that the previously observed removal of oxidative base lesions in mitochondrial DNA is initiated by the above DNA glycosylases.
Journal of Biological ChemistryMammalian Mitochondria Possess Homologous DNA Recombination Activity
277 Citations1996Bhaskar Thyagarajan, Rodolfo A. Padua +1 more
The presence of homologous recombination activity within mammalian mitochondrial extracts suggests that this process is involved in mitochondrial DNA repair.
Journal of Biological ChemistryDouble Strand Break Repair
269 Citations1997Gilbert Chu
Understanding DSB repair pathways will lead to insights for immunology and cancer, and C-NHEJ is responsible for creating the chromosomal translocations seen in cancer.
CarcinogenesisRepair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells
269 Citations1992Susan P. LeDoux, Glenn L. Wilson +4 more
It is demonstrated that it is possible not only to study mitochondrial DNA repair, but also directly to compare mitochondrial and nuclear DNA repair in the same biological sample and that repair capacity of mitochondrial DNA damage depends upon the type of lesion produced by the damaging agent.
Journal of Biological ChemistryHuman Exonuclease I Is Required for 5′ and 3′ Mismatch Repair
253 Citations2002Jochen Genschel, L. Rochelle Bazemore +1 more
The involvement of hEXOI in 3′-heteroduplex repair suggests that it has a regulatory/structural role in assembly of the3′-excision complex or that the protein possesses a cryptic 3′ to 5′ hydrolytic activity.
Journal of Cellular PhysiologyDNA mismatch repair and mutation avoidance pathways
253 Citations2002Thomas M. Marti, C Kunz +1 more
MMR‐independent pathways or factors that can process some types of mismatches in DNA are nucleotide‐excision repair (NER), some base excision repair (BER) glycosylases, and the flap endonuclease FEN‐1.
Molecular CellMechanism of 5′-Directed Excision in Human Mismatch Repair
252 Citations2003Jochen Genschel, Paul Modrich
A purified system that supports mismatch-dependent 5'-->3' excision by EXOI is developed and excision directed by a 5' strand break in HeLa nuclear extract can proceed in the absence of MutLalpha or PCNA, although 3' excison in the extract system requires both proteins.
Proceedings of the National Academy of SciencesIncreased <i>in vivo</i> apoptosis in cells lacking mitochondrial DNA gene expression
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BiochimieThe base excision repair: mechanisms and its relevance for cancer susceptibility
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GeneMitochondrial DNA repair of oxidative damage in mammalian cells
198 Citations2002Vilhelm A. Bohr, Tinna Stevnsner +1 more
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The 8-oxo-dGTPase encoded by MTH1 gene is localized in mitochondria and cytosol, mainly located in cytosolic and mitochondrial soluble fractions of Jurkat cells, a human T-cell leukemia line.
Proceedings of the National Academy of SciencesGeneration of a strong mutator phenotype in yeast by imbalanced base excision repair
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BioEssays<i>O</i><sup>6</sup>‐alkylguanine‐DNA alkyltransferase: Role in carcinogenesis and chemotherapy
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The DNA in human cells is continuously undergoing damage as consequences of both endogenous processes and exposure to exogenous agents, and there is consequently a great deal of interest in this repair system in relation to both carcinogenesis and cancer chemotherapy.
Nucleic Acids ResearchThe mitochondrial DNA polymerase as a target of oxidative damage
182 Citations2002Maria A Graziewicz
Pol gamma was detected as one of the major oxidized mitochondrial matrix proteins, with a detectable decline in polymerase activity, which may result in a reduction in mitochondrial DNA replication and repair capacities.
Nucleic Acids ResearchMismatch repair activity in mammalian mitochondria
181 Citations2003P. A. Mason
Evidence is reported consistent with a mismatch repair capability in mammalian mitochondria that exhibits some characteristics of the nuclear pathway and a hypothesis to explain the molecular mechanism of mitochondrial MMR in the light of these observations is discussed.
PubMedP53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA.
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Binding of mtT FA to cisplatin-modified DNA was significantly enhanced by p53, whereas binding to oxidized DNA was inhibited, suggesting that the interaction of p53 with mtTFA may play an important role in apoptosis.
Nucleic Acids ResearchMitochondrial DNA damage and a hypoxic response are induced by CoCl2 in rat neuronal PC12 cells
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It is found that in the presence of hypoxia-mimicking concentrations of CoCl(2), mitochondrial but not nuclear DNA damage is induced in rat neuronal, PC12 cells, the first documentation of induction of mitochondrial DNA (mtDNA) damage under these conditions.
Nucleic Acids ResearchMitoProteome: mitochondrial protein sequence database and annotation system
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By highly automating the processes of maintaining the MitoProteome Protein List and extracting relevant data from external databases, this work is able to present a dynamic database, updated frequently to reflect changes in public resources.
Progress in nucleic acid research and molecular biologyBase excision repair in nuclear and mitochondrial DNA
171 Citations2001Grigory L. Dianov, Nadja C. de Souza‐Pinto +4 more
In vitro experiments performed using rat and human mitochondrial extracts suggest that the repair incorporation during the removal of uracil in DNA occurs via the short-patch repair BER pathway, and extension of these studies suggests that DNA polymerase beta plays a critical role not only in the shortpatch repair process but also in the long-patch, PCNA-dependent pathway.
Free Radical ResearchAge-associated change in mitochondrial DNA damage
169 Citations1998Edgar K. Hudson, Barbara A. Hogue +5 more
These findings agree with other reports showing an age-associated increase in levels of mtDNA damage; however, the degree to which it increases is smaller.
Journal of Biological ChemistryActivation of Human MutS Homologs by 8-Oxo-guanine DNA Damage
167 Citations2002Anthony Mazurek, Mark Berardini +1 more
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166 Citations2001Daisuke Tsuchimoto
The results suggest thatAPE2 participates in both nuclear and mitochondrial BER and also that nuclear APE2 functions in the PCNA-dependent BER pathway.
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153 Citations1991Cathy Pettepher, Susan P. LeDoux +2 more
It is demonstrated that streptozotocin causes appreciable mitochondrial DNA damage in a dose-dependent manner and the first evidence that a repair mechanism for alkali-labile sites is present within the mitochondrion is provided.
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152 Citations2003Youri I. Pavlov, Ibrahim M. Mian +1 more
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Mutation Research/DNA RepairRepair of DNA damage in mitochondria
146 Citations1999Dennis E. Sawyer, Bennett Van Houten
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146 Citations1999Ingrun Alseth, Lars Eide +4 more
It is concluded that functions of both NTG1 and NTG2 are important for removal of oxidative DNA damage in yeast.
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144 Citations2004Mikhail Alexeyev, Susan P. LeDoux +1 more
Recent developments in aging research related to the role played by mtDNA are reviewed, both supportive and contradictory evidence is discussed.
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137 Citations2000Gwendolyn B. Sancar
Investigations looking at the repair of lesions in chromatin have begun to elucidate how DNA repair enzymes deal with damage in the context of eukaryotic chromosomes, and genetic and molecular studies of PHR1 have led to the identification of previously unknown damage-responsive transcriptional regulators.
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135 Citations1995Hiroyuki Kamiya, Hiroyuki Miura +9 more
Results indicate that OH8Ade induced misincorporation in in vitro DNA synthesis and mutations in mammalian cells.
DNA repairCharacterization of nuclease-dependent functions of Exo1p in Saccharomyces cerevisiae
131 Citations2002Phuoc T. Tran, Naz Erdeniz +2 more
It is demonstrated that full-length yeast Exo1p possesses an intrinsic 5'-3' exonuclease activity as reported previously, but also possesses a flap-endonucleaseActivity, and this study indicates that Exo 1p shares similar, but not identical structure-function relationships to other characterized members of the Rad2p family in the N and I nuclease domains.
Nature Reviews GeneticsThe curious history of yeast mitochondrial DNA
128 Citations2002Don Williamson
Forty years ago, soon after yeast mitochondrial DNA was recognized, some animal versions of mtDNA were shown to comprise circular molecules, supporting an idea that mitochondria had evolved from bacteria, and this finding generated a dogmatic belief that yeast mtDNA was also circular.
Journal of Biological ChemistryAction of Mitochondrial DNA Polymerase γ at Sites of Base Loss or Oxidative Damage
126 Citations1995Kevin G. Pinz, Shinya Shibutani +1 more
Both mitochondrial DNA lesions have the prospect of causing high rates of mutation during mtDNA replication and the effects of these lesions on the 3′ 5′ exonuclease proofreading activity of DNA polymerase were investigated.
Proceedings of the National Academy of SciencesAge-dependent deficiency in import of mitochondrial DNA glycosylases required for repair of oxidatively damaged bases
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It is shown that although the total OGG1 activity is higher in old mitochondria, a large fraction of the enzyme is stuck to the membrane in the precursor form, which could not be translocated to and processed in the mitochondrial matrix.
DNA repairFunctions of human DNA polymerases η, κ and ι suggested by their properties, including fidelity with undamaged DNA templates
123 Citations2003Thomas A. Kunkel, Youri I. Pavlov +1 more
Evidence that exonuclease-deficient polymerases copy undamaged DNA with very low fidelity and unusual error specificity is reviewed to consider the possibility that they participate in specialized DNA transactions that repair damaged DNA and/or generate mutations in the variable regions of immunoglobulin genes.
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123 Citations2001Kazuo Fujikawa
It is suggested that the 2-hydroxy-ATP hydrolyzing activity of MTH1 might prevent the perturbation of these ATP-related pathways by the oxidized ATP.
Molecular CarcinogenesisCritical DNA damage recognition functions of XPC‐hHR23B and XPA‐RPA in nucleotide excision repair
122 Citations2003Brian S. Thoma, Karen M. Vásquez
The evidence that supports damage detection by these protein complexes are compared and a model for DNA damage recognition in NER is proposed based on the current understanding of the roles these proteins may play in the processing of DNA lesions.
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122 Citations2002Thomas W. O’Rourke, Nicole Doudican +3 more
These results document the existence of recombination-independent mechanisms in addition to base excision repair to cope with oxidative mtDNA damage in Saccharomyces cerevisiae, validating yeast as a model system in which to study these important issues.
Free Radical Biology and MedicineDNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts
118 Citations2001Nadja C. de Souza‐Pinto
The results show that the repair of 8-oxodG is regulated differently in nucleus and mitochondria during the aging process, and suggests that this pathway may be up regulated during aging in mice.
PubMedThe presence of nuclear and mitochondrial uracil-DNA glycosylase in extracts of human KB cells.
112 Citations1980Corrie Anderson, Errol C. Friedberg
Evidence is presented for the presence of identifiable uracil-DNA glycosylase activity associated with the mitochondrial fraction of human KB cells within the nuclear fraction of these cells.
The EMBO JournalCloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA.
111 Citations1987F. Foury, A. Lahaye
The nuclear gene PIF of Saccharomyces cerevisiae is required for both repair of mitochondrial DNA (mtDNA) and recognition of a recombinogenic signal characterized by a 26‐bp palindromic AT sequence in the ery region of mtDNA.
Journal of Biological ChemistryTransfer of the MSH2·MSH6 Complex from Proliferating Cell Nuclear Antigen to Mispaired Bases in DNA
109 Citations2002Patrick J. Lau, Richard D. Kolodner
It is shown that PCNA and MSH2·MSH6 form a stable ternary complex with a homoduplex (G/C) DNA, but the addition of ATP or adenosine 5′-O-(thiotriphosphate) restores MSH 2· MSH6 binding to PCNA, presumably by disrupting MSH1·MSh4 binding to the heterod uplex (T/T) DNA.
Nucleic Acids ResearchDouble strand break rejoining by mammalian mitochondrial extracts
105 Citations1999Uma Lakshmipathy
The results suggest that mammalian mitochondria possess a DNA double strand break repair activity similar to that seen in the nucleus, and that this repair pathway may play a role in the generation of mitochondrial DNA deletions associated with a number of human pathologies.
Molecular and Cellular BiologyPir1p Mediates Translocation of the Yeast Apn1p Endonuclease into the Mitochondria To Maintain Genomic Stability
103 Citations2001Ratsavarinh Vongsamphanh, Pierre-Karl Fortier +1 more
It is concluded that Pir1p interacts with Apn1p, at the level of either the cytoplasm or nucleus, and facilitates Apn 1p transport into the mitochondria to repair damaged DNA.
Journal of Biological ChemistryThe Human dUTPase Gene Encodes both Nuclear and Mitochondrial Isoforms
102 Citations1997Robert D. Ladner, Salvatore J. Caradonna
These analyses demonstrate that the dUTPase isoforms are encoded by the same gene with isoform-specific transcripts arising through the use of alternative 5′ exons, the first example in humans of alternative5′ exon usage to generate differentially expressed nuclear and mitochondrial specific protein isoforms.
DNA repairA model for initial DNA lesion recognition by NER and MMR based on local conformational flexibility
101 Citations2004Richard Isaacs, H. Peter Spielmann
A model for initial detection of lesions by both NER and MMR is proposed that occurs through an indirect readout mechanism of alternative DNA conformations induced by covalent damage and base mismatches.
BiochemistryFunctional effects of cis-thymine glycol lesions on DNA synthesis in vitro
101 Citations1987James M. Clark, G. Peter Beardsley
It is suggested that increased nucleotide turnover at the site of the lesion contributes to the inhibitory effects of thymine glycol lesions on DNA synthesis in vitro, at least for polymerases such as polymerase I that have intrinsic or associated editing exonuclease functions.
CarcinogenesisRepair of alkylated purines in the hepatic DNA of mitochondria and nuclei in the rat
101 Citations1988Kevin A. Myers, R. Saffhill +1 more
It is suggested that O 6-MeG, but not O6-BuG can be repaired from mtDNA by a MT protein that is nuclear encoded and transported across the mitochondrial membrane.
Biochemical and Biophysical Research CommunicationsMouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides
100 Citations2003Jian‐Ping Cai, Tôru Ishibashi +3 more
EMBO ReportsProminent mitochondrial DNA recombination intermediates in human heart muscle
99 Citations2001Olli A. Kajander, Pekka J. Karhunen +2 more
Junctional molecules were detected in all regions of the mitochondrial genome, were found in myocardial DNA from young and old adults, but were present at lower levels in skeletal muscle and placenta, suggesting that they could represent intermediates of mtDNA repair, given their prevalence in the oxyradical‐rich environment of heart muscle mitochondria.
The EMBO JournalRecombination‐dependent mtDNA partitioning: in vivo role of Mhr1p to promote pairing of homologous DNA
98 Citations2002Feng Ling, Takehiko Shibata
A mechanism for mtDNA inheritance similar to that operating in the replication and packaging of phage DNA is suggested, indicating the strict dependence of mtDNA maintenance on recombination functions.
Journal of Biological ChemistryStructure of a Duplex DNA Containing a Thymine Glycol Residue in Solution
97 Citations1997Hsiang Chuan Kung, Philip H. Bolton
The structure of a duplex DNA containing a single thymine glycol has been determined by the combined use of NMR and restrained molecular dynamics and shows that the thymine Glycol induces a significant, localized structural change with the thyme glycol largely extrahelical.
Journal of Biological ChemistryConditional Targeting of the DNA Repair Enzyme hOGG1 into Mitochondria
94 Citations2002Lyudmila I. Rachek, Valentina Grishko +4 more
Functional studies revealed that cells containing recombinant OGG1 were more proficient at repairing oxidative damage in their mtDNA, and this increased repair led to increased cellular survival following oxidative stress.
Progress in nucleic acid research and molecular biologyEnzymology of mitochondrial base excision repair
94 Citations2001Daniel Bogenhagen, Kevin G. Pinz +1 more
It is evident that the scope of DNA repair activities undertaken within mitochondria is determined by the set of nucleus-encoded DNA repair enzymes that are capable of being imported into the organelle.
GeneticsDifferential Suppression of DNA Repair Deficiencies of Yeast <i>rad50</i>, <i>mre11</i> and <i>xrs2</i> Mutants by <i>EXO1</i> and <i>TLC1</i> (the RNA Component of Telomerase)
92 Citations2002L. Kevin Lewis, G. Karthikeyan +2 more
It is suggested that the 5'-3' exo activity of Exo1 is able to substitute for Rad50/Mre11/Xrs2 in rescission of specific classes of DSB end structures, and Gene-specific suppression by TLC1 demonstrates that components of telomerase can also impact on DSB repair pathways.
Nucleic Acids ResearchSingle-nucleotide patch base excision repair of uracil in DNA by mitochondrial protein extracts#
91 Citations1999Rob Stierum, Grigory L. Dianov +1 more
Employing restriction analysis of in vitro repaired DNA to map the repair patch size, it is demonstrated that only one nucleotide is incorporated during the repair process, in contrast to BER in the nucleus, mtBER of uracil in DNA is solely accomplished by single-nucleotide replacement.
Journal of Biological ChemistryThe Role of 3′-5′ Exonucleolytic Proofreading and Mismatch Repair in Yeast Mitochondrial DNA Error Avoidance
90 Citations1998S. Vanderstraeten, Sybille van den Brûle +2 more
The sequencing of mtDNA point mutations in the wild-type strain and in proofreading and mismatch-repair deficient mutants shows that mismatch repair contributes to elimination of the transitions while exonucleolytic proofreading preferentially repairs transversions, and more specifically A to T (or T to A) transversions.
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It was shown that poly(GT) tracts were considerably less stable than poly(AT) tracts and that alterations usually involved deletions rather than additions of repeat units, and poly( GT) tracts had similar stabilities in the mitochondria of diploid cells than in haploids.
Journal of Cellular PhysiologyH<sub>2</sub>O<sub>2</sub> induces translocation of APE/Ref‐1 to mitochondria in the Raji B‐cell line
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Proceedings of the National Academy of SciencesThe role of mismatch repair in the prevention of base pair mutations in <i>Saccharomyces cerevisiae</i>
88 Citations1998Marie C. Earley, Gray F. Crouse
It is suggested that recognition of mispairs opposite damaged bases may be a more important role for MMR in yeast than correction of errors opposite normal bases.
BiochemistryPurification of nuclear and mitochondrial uracil-DNA glycosylase from rat liver. Identification of two distinct subcellular forms
88 Citations1985John D. Domena, Dale W. Mosbaugh
Rat liver uracil-DNA glycosylase has been purified from nuclear extracts over 3000-fold to apparent homogeneity as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Nucleic Acids ResearchAntisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity
83 Citations2001Uma Lakshmipathy
It is concluded thatDNA ligase III is essential for the proper maintenance of mtDNA in cultured mammalian somatic cells and that DNA ligase IV is not present in the mitochondria and does not play a role in maintaining mtDNA integrity.
Circulation8-Oxo-dGTPase, Which Prevents Oxidative Stress-Induced DNA Damage, Increases in the Mitochondria From Failing Hearts
83 Citations2001Hiroyuki Tsutsui, Tomomi Ide +8 more
The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage.
Journal of Molecular BiologyDNA repair of UV photoproducts and mutagenesis in human mitochondrial DNA
81 Citations1997Barbara Pascucci, A. Versteegh +4 more
There is the first evidence of induction of mutations in mitochondrial DNA by treatment of human cells with a carcinogen by analysing the frequency and spectrum of spontaneous and UV-induced mutations by restriction site mutation (RSM) method in a restriction endonuclease site.
Mutation Research/DNA RepairMitochondrial localization of APE/Ref-1 in thyroid cells
81 Citations2001Gianluca Tell, Enrico Crivellato +8 more
Results suggest that a machinery capable of repairing DNA damaged by oxidative stress is present in mitochondria and mtDNA repair mechanisms may be impaired during cell transformation.
Journal of Biological ChemistryCharacterization of a Catalytically Slow AP Lyase Activity in DNA Polymerase γ and Other Family A DNA Polymerases
80 Citations2000Kevin G. Pinz, Daniel Bogenhagen
It is confirmed that DNA pol γ is an active dRP lyase and show that other members of the family A of DNA polymerases including Escherichia coli DNA pol I also possess this activity.
Mutation research. Fundamental and molecular mechanisms of mutagenesisSubstrate specificities and excision kinetics of DNA glycosylases involved in base-excision repair of oxidative DNA damage
80 Citations2003M. Dizdaroglu
The substrate specificities and excision kinetics of DNA glycosylases that have been investigated with the use of gas chromatography/mass spectrometry and DNA substrates with multiple lesions are reviewed.
Mutation Research/DNA RepairCell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA
78 Citations2000Luisa Luna, Magnar Bjørås +3 more
It is shown that the human enzyme also possesses efficient faPy DNA glycosylase activity as indicated both from studies of the purified protein and induced overexpression of the human NTH1 cDNA in HeLa cells.
Journal of Biological ChemistryCompromised Incision of Oxidized Pyrimidines in Liver Mitochondria of Mice Deficient in NTH1 and OGG1 Glycosylases
76 Citations2003Bensu Karahalıl, Nadja C. de Souza‐Pinto +3 more
Frontiers in bioscienceDNA mismatch repair and cancer
75 Citations2003Guo‐Min Li
Homologs of bacterial MutS and MutL, which are key players in the initiation steps of both the strand-specific mismatch correction and MMR-dependent apoptotic signaling, have been identified in human cells.
GliaTargeting human 8‐oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione‐induced oxidative stress
74 Citations2003Nadiya Druzhyna, Scott B. Hollensworth +3 more
Targeting the OGG repair enzyme to mitochondria reduces the release of cytochrome c from the intermitochondrial space and the activation of caspase 9 in oligodendrocytes after exposure to menadione, and appears to be a viable approach for the protection of cells against some of the deleterious effects of oxidative stress.
Annals of the New York Academy of SciencesBiological Significance of the Defense Mechanisms against Oxidative Damage in Nucleic Acids Caused by Reactive Oxygen Species: From Mitochondria to Nuclei
74 Citations2004Yusaku Nakabeppu, Daisuke Tsuchimoto +8 more
An increased susceptibility to spontaneous carcinogenesis in Mth1‐deficient mice and an alteration of MTH1 expression along with the accumulation of 8‐oxo‐dG in patients with various neurodegenerative diseases is observed.
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