The Mitochondrial p55 Accessory Subunit of Human DNA Polymerase γ Enhances DNA Binding, Promotes Processive DNA Synthesis, and Confers N-Ethylmaleimide Resistance

Lim, Susan E.; Longley, Matthew J.; Copeland, William C.

doi:10.1074/jbc.274.53.38197

Cited by 226DNA Repair MechanismsMitochondrial Function and PathologyEnzyme Structure and Function

The Mitochondrial p55 Accessory Subunit of Human DNA Polymerase γ Enhances DNA Binding, Promotes Processive DNA Synthesis, and Confers N-Ethylmaleimide Resistance

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Lim, Susan E., Longley, Matthew J., Copeland, William C.·1999·Journal of Biological Chemistry

DOI 10.1074/jbc.274.53.38197

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Abstract

Human DNA polymerase gamma is composed of a 140-kDa catalytic subunit and a smaller accessory protein variously reported to be 43-54 kDa. Immunoblot analysis of the purified, heterodimeric native human polymerase gamma complex identified the accessory subunit as 55 kDa. We isolated the full-length cDNA encoding a 55-kDa polypeptide, expressed the cDNA in Escherichia coli and purified the 55-kDa protein to homogeneity. Recombinant Hp55 forms a high affinity, salt-stable complex with Hp140 during protein affinity chromatography. Immunoprecipitation, gel filtration, and sedimentation analyses revealed a 190-kDa complex indicative of a native heterodimer. Reconstitution of Hp140.Hp55 raises the salt optimum of Hp140, stimulates the polymerase and exonuclease activities, and increases the processivity of the enzyme by several 100-fold. Similar to Hp140, isolated Hp55 binds DNA with moderate strength and was a specificity for double-stranded primer-template DNA. However, Hp140.Hp55 has a surprisingly high affinity for DNA, and kinetic analyses indicate Hp55 enhances the affinity of Hp140 for primer termini by 2 orders of magnitude. Thus the enhanced DNA binding caused by Hp55 is the basis for the salt tolerance and high processivity characteristic of DNA polymerase gamma. Observation of native DNA polymerase gamma both as an Hp140 monomer and as a heterodimer with Hp55 supports the notion that the two forms act in mitochondrial DNA repair and replication. Additionally, association of Hp55 with Hp140 protects the polymerase from inhibition by N-ethylmaleimide.

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The accessory subunit of Pol γ is required for enhanced DNA processivity by augmenting the affinity of the catalytic subunit for DNA.
“The accessory subunit is required for enhanced DNA processivity by augmenting the affinity of the catalytic subunit for DNA (Lim et al., 1999; Young et al., 2015).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Lim et al., 1999
PolG2 functions to enhance processivity of DNA replication by augmenting the binding of PolG to DNA.
“PolG2 is a 110 kDa homodimeric accessory subunit for the catalytic subunit PolG (Carrodeguas et al., 2001) that functions to enhance processivity of DNA replication by augmenting the binding of PolG to DNA (Lim et al., 1999).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Lim et al., 1999

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de Souza-Pinto, N. C., Wilson, D. M., Stevnsner, T., & Bohr, V. A. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.03.011 · Cited by 102 · see citing works
Oxidative damage diminishes mitochondrial DNA polymerase replication fidelity
Anderson, A. P., Luo, X., Russell, W. K., & Yin, Y. W. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1018 · Cited by 100 · see citing works
New features of mitochondrial DNA replication system in yeast and man
Lecrenier, N., & Foury, F. (2000) · Gene · doi:10.1016/s0378-1119(00)00107-4 · Cited by 98 · see citing works
Modulation of the W748S mutation in DNA polymerase γ by the E1143G polymorphismin mitochondrial disorders
Chan, S. S. L., Longley, M. J., & Copeland, W. C. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl424 · Cited by 96 · see citing works
DNA Polymerase Gamma in Mitochondrial DNA Replication and Repair
Copeland, W. C., & Longley, M. J. (2003) · The Scientific World JOURNAL · doi:10.1100/tsw.2003.09 · Cited by 91 · see citing works
The DNA polymerase Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine
Graziewicz, M. A., Bienstock, R. J., & Copeland, W. C. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm227 · Cited by 93 · see citing works
“The accessory subunit (p55) was purified to homogeneity from E. coli, and the heterotrimeric forms of the polymerase were reconstituted as previously described ( 59 ).”
Method
Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance
Young, M. J. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00074 · Cited by 87 · see citing works
“The homodimeric Polγ p55 subunit imparts high processivity onto the holoenzyme by increasing the binding affinity to DNA (Lim et al., 1999; Young et al., 2015).”
Background
Trace amounts of 8-oxo-dGTP in mitochondrial dNTP pools reduce DNA polymerase replication fidelity
Pursell, Z. F., McDonald, J., Mathews, C. K., & Kunkel, T. A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn062 · Cited by 87 · see citing works
“These proteins were purified separately to homogeneity and then used as described previously ( 28 ,29).”
Structural Determinants in Human DNA Polymerase γ Account for Mitochondrial Toxicity from Nucleoside Analogs
Lim, S. E., Ponamarev, M. V., Longley, M. J., & Copeland, W. C. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00405-4 · Cited by 85 · see citing works
The Mitochondrial DNA Polymerase in Health and Disease
Copeland, W. C. (2009) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-3471-7_11 · Cited by 85 · see citing works
“The accessory subunit is a 55 kDa protein (p55) required for tight DNA binding and processive DNA synthesis ( Lim et al., 1999 ).”
Background
Mitochondrial DNA maintenance: an appraisal
Akhmedov, A. T., & Marı́n-Garcı́a, J. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2532-x · Cited by 82 · see citing works
The accessory subunit of mitochondrial DNA polymerase γ determines the DNA content of mitochondrial nucleoids in human cultured cells
Re, M. D., Sembongi, H., He, J., Reyes, A., Yasukawa, T., Martinsson, P., Bailey, L., Goffart, S., Boyd-Kirkup, J. D., Wong, T. S., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp614 · Cited by 82 · see citing works
“POLGb’s affinity for dsDNA was greater than we observed in one report (20), but similar to another study (17).”
BackgroundResult
Polg2 is essential for mammalian embryogenesis and is required for mtDNA maintenance
Humble, M. M., Young, M. J., Foley, J. F., Pandiri, A. R., Travlos, G. S., & Copeland, W. C. (2013) · Human Molecular Genetics · doi:10.1093/hmg/dds506 · Cited by 78 · see citing works
The p53 Pathway Promotes Efficient Mitochondrial DNA Base Excision Repair in Colorectal Cancer Cells
Chen, D., Yu, Z., Zhu, Z., & Lopez, C. D. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4103 · Cited by 77 · see citing works
“Incubation of extracts with N-methylmalaemide, an inhibitor of the 140 kDa catalytic subunit of mtDNA polymerase-g (50), attenuated incorporation (Fig.”
Method
A Novel Processive Mechanism for DNA Synthesis Revealed by Structure, Modeling and Mutagenesis of the Accessory Subunit of Human Mitochondrial DNA Polymerase
Fan, L., Kim, S., Farr, C. L., Schaefer, K. T., Randolph, K. M., Tainer, J. A., & Kaguni, L. S. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.02.073 · Cited by 74 · see citing works
Ribonucleotide Discrimination and Reverse Transcription by the Human Mitochondrial DNA Polymerase
Kasiviswanathan, R., & Copeland, W. C. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.252460 · Cited by 71 · see citing works
Self-citation
Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers
Michiels, S., Danoy, P., Dessen, P., Bera, A., Boulet, T., Bouchardy, C., Lathrop, M. G., Sarasin, A. R., & Benhamou, S. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm111 · Cited by 71 · see citing works
“From those, POLG2 was one of the two genes that showed potential haplotype association with H-N, together with RPA1 (another subunit of the single-strand binding complex replication protein A). POLG2 encodes a 55 kDa protein that interacts with the catalytic activity of the DNA polymerase gamma necessary for replicati…”
Background
Oxidative DNA damage stalls the human mitochondrial replisome
Stojkovič, G., Makarova, А. V., Wanrooij, P. H., Forslund, J. M. E., Burgers, P., & Wanrooij, S. (2016) · Scientific Reports · doi:10.1038/srep28942 · Cited by 71 · see citing works
Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase γ associated with progressive external ophthalmoplegia
Stuart, G. R., Santos, J. H., Strand, M. K., Houten, B. V., & Copeland, W. C. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi454 · Cited by 71 · see citing works
“In animal cells, the pol g accessory subunit is a DNA-binding factor and is required for highly processive mtDNA synthesis ( 44 ).”
Background
Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase
Szymański, M. R., Kuznetsov, V. B., Shumate, C. K., Meng, Q., Lee, Y., Patel, G., Patel, S. S., & Yin, Y. W. (2015) · The EMBO Journal · doi:10.15252/embj.201591520 · Cited by 67 · see citing works
“Indeed, Pol c A alone displays low processivity (Graves et al , 1998; Lim et al , 1999).”
Mitochondrial dysfunction and nucleoside reverse transcriptase inhibitor therapy: experimental clarifications and persistent clinical questions
Lewis, W. (2003) · Antiviral Research · doi:10.1016/s0166-3542(03)00069-x · Cited by 70 · see citing works
155th ENMC workshop: Polymerase gamma and disorders of mitochondrial DNA synthesis, 21–23 September 2007, Naarden, The Netherlands
Chinnery, P. F., & Zeviani, M. (2007) · Neuromuscular Disorders · doi:10.1016/j.nmd.2007.11.005 · Cited by 67 · see citing works
Biochemical analysis of human POLG2 variants associated with mitochondrial disease
Young, M. J., Longley, M. J., Li, F.-Y., Kasiviswanathan, R., Wong, L.-J., & Copeland, W. C. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr209 · Cited by 66 · see citing works
“The salt-dependent stimulation of p140 by p55 has been demonstrated previously with the exonuclease proficient form of p140 on poly(rA)†oligo(dT)12 – 18 (10), and we saw almost identical stimulation of the exonuclease deficient form of pol g in this study (Fig.”
Influential
Mitochondrial DNA degradation: A quality control measure for mitochondrial genome maintenance and stress response
Zhao, L. (2019) · The Enzymes · doi:10.1016/bs.enz.2019.08.004 · Cited by 63 · see citing works
Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells
Sun, X., Johnson, J. L., & John, J. C. S. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky339 · Cited by 62 · see citing works
“Taqman assays used in the Fluidigm qPCR arrays Gene name Taqman assay number Gene name Taqman assay number 18SrRNA Hs99999901_s1 MT-ND2 Hs02596874_g1 Actb Hs99999903_m1 MT-ND3 Hs02596875_s1 ADGRB1 Hs00181777_m1 MT-ND4 Hs02596876_g1 AGAP3 Hs01553103_g1 MT-ND4L Hs02596877_g1 AGPAT4 Hs01088853_m1 MT-ND5 Hs02596878_g1 ASL…”
BackgroundInfluential
Analysis of mutant DNA polymerase γ in patients with mitochondrial DNA depletion
Taanman, J., Rahman, S., Pagnamenta, A. T., Morris, A. A. M., Bitner-Glindzicz, M. A. K., Wolf, N. I., Leonard, J. V., Clayton, P. T., & Schapira, A. H. V. (2008) · Human Mutation · doi:10.1002/humu.20852 · Cited by 61 · see citing works
DNA Binding Properties of Human pol γB
Carrodeguas, J. A., Pinz, K. G., & Bogenhagen, D. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207030200 · Cited by 59 · see citing works
“Our results suggest that the presence of a 5 overhang in the primertemplate used by Lim et al. (1999) probably did not influence the binding. pol B has shown a similar ability to bind other duplex fragments longer than ds47 (data not shown), suggesting that DNAs must exceed a minimal size between…”
Background
Consequences of compromised mitochondrial genome integrity
Gustafson, M. A., Sullivan, E. D., & Copeland, W. C. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102916 · Cited by 58 · see citing works
Mitochondrial genetic variation is enriched in G-quadruplex regions that stall DNA synthesis in vitro.
Butler, T. J., Estep, K. N., Sommers, J. A., Maul, R., Moore, A., Bandinelli, S., Cucca, F., Tuke, M., Wood, A., Bharti, S., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa043 · Cited by 54 · see citing works
“The observation that reactions with both polymerases produced DNA products resembling those produced by Pol γ alone is consistent with reports that Pol γ binds DNA with high affinity, whereas PrimPol exhibits weaker binding (40,41).”
Result
DNA base excision repair activities and pathway function in mitochondrial and cellular lysates from cells lacking mitochondrial DNA
Stuart, J. A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh533 · Cited by 58 · see citing works
“Indeed, other factors including the polymerase g accessory subunit affect polymerase g’s interaction with oligonucleotides ( 22 ,23).”
Background
Progressive External Ophthalmoplegia and Vision and Hearing Loss in a Patient With Mutations in POLG2 and OPA1
Ferraris, S., Clark, S., Garelli, E., Davidzon, G., Moore, S. A., Kardon, R. H., Bienstock, R. J., Longley, M. J., Mancuso, M., Ríos, P. G., et al. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.9 · Cited by 57 · see citing works
“The G416A was grown, expressed, purified, and stored, as described previously.(10,14)”
MethodInfluential
Defects of Mitochondrial DNA Replication
Copeland, W. C. (2014) · Journal of Child Neurology · doi:10.1177/0883073814537380 · Cited by 54 · see citing works
“This also demonstrates that disruption of exonuclease activity is not embryonic lethal, as compared to the knockout of the entire POLG gene function.55 POLG2, the Gene for the p55 Accessory Subunit of Pol γ Using a partial human POLG2 clone identified during the cloning of the Drosophila accessory subunit,56 the full-…”
BackgroundMethodInfluential
Nuclear Transfer: Preservation of a Nuclear Genome at the Expense of Its Associated mtDNA Genome(s)
Bowles, E. J., Campbell, K., & John, J. C. S. (2007) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(06)77010-7 · Cited by 54 · see citing works
The accessory subunit of DNA polymerase γ is essential for mitochondrial DNA maintenance and development in Drosophila melanogaster
Iyengar, B. G., Luo, N., Farr, C. L., Kaguni, L. S., & Campos, A. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.072664899 · Cited by 53 · see citing works
Nucleotide incorporation by human DNA polymerase opposite benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyguanosine and deoxyadenosine
Graziewicz, M. A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh213 · Cited by 52 · see citing works
“The recombinant human accessory subunit (p55) was puri®ed to homogeneity from Escherichia coli and the heterodimeric forms of the polymerase were reconstituted as previously described (28).”
Method
A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA
Sanchez-Contreras, M., Sweetwyne, M. T., Kohrn, B. F., Tsantilas, K. A., Hipp, M. J., Schmidt, E. K., Fredrickson, J., Whitson, J. A., Campbell, M., Rabinovitch, P., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab901 · Cited by 42 · see citing works
Disease Mutations in the Human Mitochondrial DNA Polymerase Thumb Subdomain Impart Severe Defects in Mitochondrial DNA Replication
Kasiviswanathan, R., Longley, M. J., Chan, S. S. L., & Copeland, W. C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.011940 · Cited by 52 · see citing works
Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders.
Copeland, W. C., Ponamarev, M. V., Nguyen, D., Kunkel, T. A., & Longley, M. J. (2003) · Acta Biochimica Polonica · doi:10.18388/abp.2003_3723 · Cited by 51 · see citing works
“nents, where subsequent to actions of uracil-DNA glycosylase and AP endonuclease, pol can fill a single nucleotide gap in the presence of a 5 terminal deoxyribose phosphate (dRP) flap (Longley et al., 1998).”
BackgroundMethodInfluential
Binding parameters and thermodynamics of the interaction of the human cytomegalovirus DNA polymerase accessory protein, UL44, with DNA: implications for the processivity mechanism
Loregian, A., Sinigalia, E., Mercorelli, B., Palù, G., & Coen, D. M. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm506 · Cited by 50 · see citing works
“cognate catalytic subunit in the absence of DNA and stimulates its polymerizing activity on activated DNA templates (23, 43 ).”
Background
Aging-associated accumulation of mitochondrial DNA mutations in tumor origin
Kong, M., Guo, L., Xu, W., He, C., Jia, X., Zhao, Z., & Gu, Z. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac014 · Cited by 48 · see citing works
mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae
Stumpf, J. D., Bailey, C. M., Spell, D., Stillwagon, M., Anderson, K. S., & Copeland, W. C. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq089 · Cited by 48 · see citing works
Biolayer Interferometry: A Novel Method to Elucidate Protein–Protein and Protein–DNA Interactions in the Mitochondrial DNA Replisome
Ciesielski, G. L., Hytönen, V. P., & Kaguni, L. S. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3040-1_17 · Cited by 47 · see citing works
Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol γ
Euro, L., Farnum, G. A., Palin, E., Suomalainen, A., & Kaguni, L. S. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr618 · Cited by 46 · see citing works
“The accessory subunit, Pol gB, serves as a processivity factor, enhancing the DNA-binding affinity and catalytic activities of Pol gA (5,6).”
Human Mitochondrial DNA Polymerase γ Exhibits Potential for Bypass and Mutagenesis at UV-induced Cyclobutane Thymine Dimers
Kasiviswanathan, R., Gustafson, M. A., Copeland, W. C., & Meyer, J. N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.306852 · Cited by 46 · see citing works
“The accessory subunit is a 55-kDa protein (p55) required for tight DNA binding and processive DNA synthesis (24).”
Background
The interface of transcription and DNA replication in the mitochondria
Kasiviswanathan, R., Collins, T., & Copeland, W. C. (2011) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2011.12.005 · Cited by 46 · see citing works
“In addition, the processivity of the catalytic subunit is enhanced as much as 50-fold upon interaction with the accessory subunit [30].”
BackgroundInfluential
Increase in mitochondrial DNA mutations impairs retinal function and renders the retina vulnerable to injury
Kong, Y. X. G., Bergen, N. V., Trounce, I. A., Bui, B. V., Chrysostomou, V., Waugh, H. S., Vingrys, A. J., & Crowston, J. G. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00690.x · Cited by 43 · see citing works
“One enzyme central to the process of mtDNA replication is polymerase c (PolG; Kaguni, 2004; Graziewicz et al., 2006), which consists of a catalytic subunit with polymerase and exonuclease activity and a small accessory subunit that enhances binding (Lim et al., 1999).”
Background
R964C Mutation of DNA Polymerase γ Imparts Increased Stavudine Toxicity by Decreasing Nucleoside Analog Discrimination and Impairing Polymerase Activity
Bailey, C. M., Kasiviswanathan, R., Copeland, W. C., & Anderson, K. S. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01659-08 · Cited by 45 · see citing works
“As such, WT and R964C Pol catalytic subunits (exonuclease deficient) and the accessory subunit were expressed, purified, and reconstituted as described previously (10, 15 , 17).”
BackgroundMethod
POLB: A new role of DNA polymerase beta in mitochondrial base excision repair
Kaufman, B. A., & Houten, B. V. (2017) · DNA repair · doi:10.1016/j.dnarep.2017.11.002 · Cited by 43 · see citing works
Functional Roles of the N- and C-Terminal Regions of the Human Mitochondrial Single-Stranded DNA-Binding Protein
Oliveira, M. T., & Kaguni, L. S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015379 · Cited by 43 · see citing works
“pol γ activity is stimulated ∼2 fold as the concentration of KCl in the reaction increases from 20 to 100 mM, in agreement with previously published data”
Result
Mitochondrial DNA replication, nucleoside reverse-transcriptase inhibitors, and AIDS cardiomyopathy
Lewis, W. (2003) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2003.3b · Cited by 43 · see citing works

A Novel Processive Mechanism for DNA Synthesis Revealed by Structure, Modeling and Mutagenesis of the Accessory Subunit of Human Mitochondrial DNA Polymerase
Fan, L., Kim, S., Farr, C. L., Schaefer, K. T., Randolph, K. M., Tainer, J. A., & Kaguni, L. S. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.02.073 · Cited by 74 · see citing works
Each Monomer of the Dimeric Accessory Protein for Human Mitochondrial DNA Polymerase Has a Distinct Role in Conferring Processivity
Lee, Y., Lee, S., Demeler, B., Molineux, I. J., Johnson, K. A., & Yin, Y. W. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.062752 · Cited by 57 · see citing works
The Accessory Subunit of Xenopus laevis Mitochondrial DNA Polymerase γ Increases Processivity of the Catalytic Subunit of Human DNA Polymerase γ and Is Related to Class II Aminoacyl-tRNA Synthetases
Carrodeguas, J. A., Kobayashi, R., Lim, S. E., Copeland, W. C., & Bogenhagen, D. F. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4039 · Cited by 108 · see citing works
Stimulation of DNA polymerase gamma by a mitochondrial single-strand DNA binding protein.
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The EM structure of human DNA polymerase γ reveals a localized contact between the catalytic and accessory subunits
Yakubovskaya, E., Lukin, M., Chen, Z., Berriman, J. A., Wall, J. S., Kobayashi, R., Kisker, C., & Bogenhagen, D. F. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601843 · Cited by 18 · see citing works

Authors: Lim, S. E., Longley, M. J., & Copeland, W. C.
Affiliations: National Institutes of Health (US)
Corresponding author: Copeland, William C.
ORCID: Longley, Matthew J.
Copeland, William C.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1999-12
Volume: 274
Issue: 53
Pages: 38197-38203
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.274.53.38197
OpenAlex: W2001256046
Cited by: 226
References: 30
Citations by year: 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 10 · 2019: 3 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 13
FWCI: 2.97
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7617 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institute of Environmental Health Sciences
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords: DNA polymerase gamma, heterodimer, DNA binding, processivity, exonuclease activity, salt tolerance, mitochondrial DNA repair, mitochondrial DNA replication, recombinant protein purification
MeSH terms: DNA Polymerase gamma, Base Sequence, DNA, DNA-Directed DNA Polymerase, DNA Replication, Escherichia coli, Ethylmaleimide, Humans, Mitochondria, Molecular Sequence Data, Protein Binding, Recombinant Proteins, Sodium Chloride, DNA Primers, DNA, Complementary, Dimerization, Catalytic Domain

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The Mitochondrial p55 Accessory Subunit of Human DNA Polymerase γ Enhances DNA Binding, Promotes Processive DNA Synthesis, and Confers N-Ethylmaleimide Resistance

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