Crystal Structure and Deletion Analysis Show that the Accessory Subunit of Mammalian DNA Polymerase γ, PolγB, Functions as a Homodimer
Open accessAbstract
Polymerase gamma, which replicates and repairs mitochondrial DNA, requires the Pol gamma B subunit for processivity. We determined the crystal structure of mouse Pol gamma B, a core component of the mitochondrial replication machinery. Pol gamma B shows high similarity to glycyl-tRNA synthetase and dimerizes through an unusual intermolecular four-helix bundle. A human Pol gamma B mutant lacking the four-helix bundle failed to dimerize in solution or to stimulate the catalytic subunit Pol gamma A, but retained the ability to bind with Pol gamma A to a primer-template construct, indicating that the functional holoenzyme contains two Pol gamma B molecules. Other mutants retained stimulatory activity but lost the ability to bind folded ssDNA. These results suggest that the Pol gamma B dimer contains distinct sites for Pol gamma A binding, dimerization, and DNA binding.
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PolG2 is a 110 kDa homodimeric accessory subunit for the catalytic subunit PolG.
“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 Carrodeguas et al., 2001
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581 · see citing works
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
Kraulis, P. J. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891004399 · Cited by 14,011 · see citing works
Jones, T. A., Zou, J.-Y., Cowan, S. W., & Kjeldgaard, M. (1991) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767390010224 · Cited by 12,650 · see citing works
Nicholls, A. O., Sharp, K. A., & Honig, B. H. (1991) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340110407 · Cited by 5,253 · see citing works
Automated MAD and MIR structure solution
Terwilliger, T. C., & Berendzen, J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444999000839 · Cited by 3,038 · see citing works
Raster3D Version 2.0. A program for photorealistic molecular graphics
Merritt, E. A., & Murphy, M. E. P. (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994006396 · Cited by 2,531 · see citing works
Automated protein model building combined with iterative structure refinement.
Perrakis, A., Morris, R. J., & Lamzin, V. S. (1999) · Nature Structural Biology · doi:10.1038/8263 · Cited by 2,423 · see citing works
Sparse matrix sampling: a screening method for crystallization of proteins
Jancarik, J., & Kim, S. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891004430 · Cited by 2,043 · see citing works
The atomic structure of protein-protein recognition sites 1 1Edited by A. R. Fersht
Conte, L. L., Chothia, C., & Janin, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2439 · Cited by 1,967 · see citing works
Fortelle, E. D. L., & Bricogne, G. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)76073-7 · Cited by 1,893 · see citing works
Computational method to predict mitochondrially imported proteins and their targeting sequences.
Claros, M. G., & Vincens, P. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.00779.x · Cited by 1,736 · see citing works
Dali: a network tool for protein structure comparison
Holm, L., & Sander, C. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89105-7 · Cited by 1,462 · see citing works
Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution
Doublié, S., Tabor, S., Long, A. M., Richardson, C. C., & Ellenberger, T. (1998) · Nature · doi:10.1038/34593 · Cited by 1,177 · see citing works
Hendrickson, W. A., Horton, J. R., & LeMaster, D. M. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08287.x · Cited by 1,015 · see citing works
DNA Polymerases: Structural Diversity and Common Mechanisms
Steitz, T. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.25.17395 · Cited by 848 · see citing works
Kong, X., Onrust, R., O’Donnell, M. E., & Kuriyan, J. (1992) · Cell · doi:10.1016/0092-8674(92)90445-i · Cited by 754 · see citing works
Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy
Arnaudo, E., Shanske, S., DiMauro, S., Schon, E. A., Moraes, C. T., Schon, E. A., & Dalakas, M. C. (1991) · The Lancet · doi:10.1016/0140-6736(91)91294-5 · Cited by 504 · see citing works
Structure of CheA, a Signal-Transducing Histidine Kinase
Bilwes, A. M., Alex, L. A., Crane, B. R., & Simon, M. I. (1999) · Cell · doi:10.1016/s0092-8674(00)80966-6 · Cited by 476 · see citing works
Anastassis Perrakis, A., Sixma, T. K., Wilson, K. S., & Lamzin, V. S. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444997005696 · Cited by 443 · see citing works
Tabor, S., Huber, H. E., & Richardson, C. C. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47718-6 · Cited by 407 · see citing works
The design and implementation ofSnBversion 2.0
Weeks, C. M., & Miller, R. (1999) · Journal of Applied Crystallography · doi:10.1107/s0021889898010504 · Cited by 388 · see citing works
Building a Replisome from Interacting Pieces
Shamoo, Y. E., & Steitz, T. A. (1999) · Cell · doi:10.1016/s0092-8674(00)81647-5 · Cited by 363 · see citing works
Knippers, R. (1970) · Nature · doi:10.1038/2281050a0 · Cited by 323 · see citing works
Sankaranarayanan, R., Dock‐Brégeon, A., Romby, P., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80746-1 · Cited by 313 · see citing works
Wallace, D. C. (1995) · PubMed Central · Cited by 264 · see citing works
Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ.
Inouye, M., Ikura, M., Tomomori, C., et al. (1999) · Nature Structural Biology · doi:10.1038/11495 · Cited by 239 · see citing works
Lim, S. E., Longley, M. J., & Copeland, W. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.53.38197 · Cited by 226 · see citing works
Structural and functional similarities of prokaryotic and eukaryotic DNA polymerase sliding clamps
Kelman, Z., & O’Donnell, M. E. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.18.3613 · Cited by 178 · see citing works
Simpson, M. V., Chin, C. D., Keilbaugh, S. A., Lin, T., & Prusoff, W. H. (1989) · Biochemical Pharmacology · doi:10.1016/0006-2952(89)90245-1 · Cited by 169 · see citing works
Lewis, W., Levine, E. S., Griniuvienė, B., Tankersley, K. O., Colacino, J. M., Sommadossi, J., Watanabe, K. A., & Perrino, F. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3592 · Cited by 169 · see citing works
Crystal structure of the DNA polymerase processivity factor of T4 bacteriophage
Moarefi, I., Jeruzalmi, D., Turner, J., O’Donnell, M. E., & Kuriyan, J. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3511 · Cited by 169 · see citing works
Zuccola, H. J., Filman, D. J., Coen, D. M., & Hogle, J. M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80422-0 · Cited by 151 · see citing works
Human Mitochondrial DNA Polymerase Holoenzyme: Reconstitution and Characterization
Johnson, A. A., Tsai, Y., Graves, S. W., & Johnson, K. A. (2000) · Biochemistry · doi:10.1021/bi992104w · Cited by 147 · see citing works
Purification and identification of subunit structure of the human mitochondrial DNA polymerase.
Gray, H. B., & Wong, T. W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42629-4 · Cited by 140 · see citing works
Four helix bundle diversity in globular proteins
Harris, N. L., Presnell, S., & Cohen, F. E. (1994) · Journal of Molecular Biology · doi:10.1016/0022-2836(94)90063-9 · Cited by 140 · see citing works
Wernette, C. M., & Kaguni, L. S. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)66938-8 · Cited by 136 · see citing works
Crystal structure of glycyl‐tRNA synthetase from Thermus thermophilus.
Logan, D. T., Mazauric, M., Kern, D., & Moras, D. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00089.x · Cited by 122 · see citing works
Varughese, K. I., Madhusudan, Zhou, X. Z., Whiteley, J. M., & Hoch, J. A. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80148-3 · Cited by 112 · see citing works
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
Self-citationMitochondrial DNA polymerases from yeast to man: a new family of polymerases.
Lecrenier, N., van der Bruggen, P., & Foury, F. (1997) · Gene · doi:10.1016/s0378-1119(96)00663-4 · Cited by 100 · see citing works
Yaremchuk, A. D., Cusack, S., & Tukalo, M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.17.4745 · Cited by 93 · see citing works
Fan, L., Sanschagrin, P. C., Kaguni, L. S., & Kuhn, L. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9527 · Cited by 89 · see citing works
Eriksson, S., Xu, B., & Clayton, D. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18929 · Cited by 73 · see citing works
Weißhart, K., Chow, C. S., & Coen, D. M. (2006) · Journal of Virology · doi:10.1128/jvi.01174-06 · Cited by 54 · see citing works
Weißhart, K., Chow, C. S., & Coen, D. M. (1999) · Journal of Virology · doi:10.1128/jvi.73.1.55-66.1999 · Cited by 51 · see citing works
Ye, F. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.8.1481 · Cited by 50 · see citing works
Carrodeguas, J. A. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.5.1237 · Cited by 49 · see citing works
Self-citationYeast mitochondrial DNA polymerase is related to the family A DNA polymerases
Ito, J., & Braithwaite, D. K. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.22.6716 · Cited by 48 · see citing works
Subunit Structure of Mitochondrial DNA Polymerase from Drosophila Embryos
Olson, M. W., Wang, Y., Elder, R. H., & Kaguni, L. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.48.28932 · Cited by 40 · see citing works
[1] Shake-and-bake: An algorithm for automatic solution ab initio of crystal structures
Hauptman, H. A. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)77003-4 · Cited by 37 · see citing works
Glycyl‐tRNA synthetase from Thermus thermophilus
Mazauric, M., Keith, G., Logan, D. T., et al. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2510744.x · Cited by 32 · see citing works
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Hübscher, U., Maga, G., & Spadari, S. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.090501.150041 · Cited by 691 · see citing works
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Falkenberg, M., Gaspari, M., Rantanen, A., Trifunovic, A., Larsson, N.-G., & Gustafsson, C. M. (2002) · Nature Genetics · doi:10.1038/ng909 · Cited by 598 · see citing works
DNA Polymerase γ, The Mitochondrial Replicase
Kaguni, L. S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161455 · Cited by 414 · see citing works
DNA Polymerase γ in Mitochondrial DNA Replication and Repair
Graziewicz, M. A., Longley, M. J., & Copeland, W. C. (2006) · Chemical Reviews · doi:10.1021/cr040463d · Cited by 301 · see citing works
Longley, M. J., Nguyen, D., Kunkel, T. A., & Copeland, W. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105230200 · Cited by 270 · see citing works
Bebenek, K., & Kunkel, T. A. (2004) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(04)69005-x · Cited by 258 · see citing works
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Longley, M. J., Clark, S., Yu Wai Man, C., Hudson, G., Durham, S. E., Taylor, R. W., Nightingale, S., Turnbull, D. M., Copeland, W. C., & Chinnery, P. F. (2006) · The American Journal of Human Genetics · doi:10.1086/504303 · Cited by 248 · see citing works
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
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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
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- Authors
- Carrodeguas, J. A., Theis, K., Bogenhagen, D. F., & Kisker, C.
- Affiliations
- Stony Brook University (US)
- Corresponding author
- Kisker, Caroline
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 7
- Issue
- 1
- Pages
- 43-54
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1978422652
- Cited by
- 150
- References
- 54
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2021: 1 · 2020: 7 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 10 · 2015: 10 · 2014: 1 · 2013: 4 · 2012: 8
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM029681, GM581980, GM29681)
- National Institute of Environmental Health Sciences (ES04068, P01ES004068)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- DNA polymerase gamma, auxiliary subunits, homodimer, four-helix bundle, mitochondrial DNA replication, DNA repair, polymerase processivity, DNA binding, crystal structure, deletion mutants
- MeSH terms
- DNA Polymerase gamma, Amino Acid Sequence, Animals, Binding Sites, Crystallography, DNA-Directed DNA Polymerase, DNA Replication, DNA, Single-Stranded, Glycine-tRNA Ligase, Humans, Mammals, Mitochondria, Molecular Sequence Data, Surface Properties, Water, Gene Deletion, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Folding, Dimerization, Mice
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