The EM structure of human DNA polymerase γ reveals a localized contact between the catalytic and accessory subunits

EMBO Journal

Volumn 26, Issue 19, 2007, Pages 4283-4291

  Yakubovskaya, Elena ^a   Lukin, Mark ^a   Chen, Zhixin ^a   Berriman, John ^b,f   Wall, Joseph S ^c   Kobayashi, Ryuji ^d   Kisker, Caroline ^e   Bogenhagen, Daniel F ^a  

^a STONY BROOK UNIVERSITY   (United States)

^b NEW YORK STRUCTURAL BIOLOGY CENTER   (United States)

^c BROOKHAVEN NATIONAL LABORATORY   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e UNIVERSITY OF WÜRZBURG   (Germany)

^f NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

Author keywords

DNA polymerase ; Electron microscopy; Mitochondrial DNA; Processivity; Replication

Indexed keywords

DNA DIRECTED DNA POLYMERASE ALPHA; DNA DIRECTED DNA POLYMERASE BETA; DNA DIRECTED DNA POLYMERASE GAMMA; HOLOENZYME; SOLVENT;

AGING; ARTICLE; BETA CHAIN; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA CLEAVAGE; ELECTRON MICROSCOPY; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME STRUCTURE; MITOCHONDRIAL DNA REPLICATION; PRIORITY JOURNAL; STAINING; STRUCTURE ANALYSIS;

EID: 34948819776     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.1038/sj.emboj.7601843     Document Type: Article

References (35)

1. Boskovic J, Rivera-Calzada A, Maman JD, Chacon P, Willison KR, Pearl LH, Llorca O (2003) Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J 22: 5875-5882
2. Brink J, Ludtke SJ, Kong Y, Wakil SJ, Ma J, Chiu W (2004) Experimental verification of conformational variation of human fatty acid synthase as predicted by normal mode analysis. Structure 12: 185-191
3. Carrodeguas JA, Bogenhagen DF (2000) Protein sequences conserved in prokaryotic aminoacyl-tRNA synthetases are important for the activity of the processivity factor of human mitochondrial DNA polymerase. Nucleic Acids Res 28: 1237-1244
4. Carrodeguas JA, Kobayashi R, Lim SE, Copeland WC, Bogenhagen DF (1999) The accessory subunit of X. laevis mitochondrial DNA polymerase γ increases processivity of the catalytic subunit of human DNA polymerase γ and is related to class II amino acyl tRNA synthetases. Mol Cell Biol 19: 4039-4046
5. Carrodeguas JA, Theis K, Bogenhagen DF, Kisker C (2001) Crystal structure and deletion analysis show that the accessory subunit of mammalian DNA polymerase γ, polγB, functions as a homodimer. Mol Cell 7: 43-54
6. Chan SSL, Longley MJ, Copeland WC (2005) The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit. J Biol Chem 280: 31341-31346
7. Doublie S, Tabor S, Long AM, Richardson CC, Ellenberger T (1998) Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Nature 391: 251-258
8. Fan L, Kim S, Farr CL, Schaefer KT, Randolph KM, Tainer JA, Kaguni LS (2006) A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase. J Mol Biol 358: 1229-1243
9. Frank J, Radermacher M, Penczek P, Zhu J, Li Y, Ladjadi M, Leith A (1996) SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields. J Struct Biol 116: 190-199
10. Graziewicz MA, Longley MJ, Bienstock RJ, Zeviani M, Copeland WC (2004) Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external opthalmoplegia. Nat Struct Mol Biol 11: 770-776
11. Graziewicz M, Longley M, Copeland W (2006) DNA polymerase γ in mitochondrial DNA replication and repair. Chem Rev 106: 383-405
12. Griffith J, Michalowski S, Makhov A (1999) Electron microscopy of DNA-protein complexes and chromatin. Meth Enzymol 304: 214-230
13. Hainfeld J (1987) A small gold-conjugated antibody label: improved resolution for electron microscopy. Science 236: 450-453
14. Henderson R (2004) Realizing the potential of electron cryo-microscopy. Q Rev Biophys 37: 3-13
15. Ito J, Braithwaite D (1990) Yeast mitochondrial DNA polymerase is related to the family A DNA polymerases. Nucleic Acids Res 18: 6716
16. Johnson AA, Tsai Y-c, Graves SW, Johnson KA (2000) Human mitochondrial DNA polymerase holoenzyme: reconstitution and characterization. Biochemistry 39: 1702-1708
17. Kaguni LS (2004) DNA polymerase γ, the mitochondrial replicase. Annu Rev Biochem 73: 293-320
18. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla T (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309: 481-484
19. Longley MJ, Graziewicz MA, Bienstock RJ, Copeland WC (2005) Consequences of mutations in human DNA polymerase γ. Gene 354: 125-131
20. Longley MJ, Nguyen D, Kunkel TA, Copeland WC (2001) The fidelity of human DNA polymerase γ with and without exonucleolytic proofreading and the p55 accessory subunit. J Biol Chem 276: 38555-38562
21. Ludtke SJ, Baldwin PR, Chiu W (1999) EMAN: semiautomated software for high-resolution single-particle reconstructions. J Struct Biol 128: 82-97
22. Miyata T, Oyama T, Mayanagi K, Ishino S, Ishino Y, Morikawa K (2004) The clamp-loading complex for processive DNA replication. Nat Struct Mol Biol 11: 632-636
23. Miyata T, Suzuki H, Oyama T, Mayanagi K, Ishino Y, Morikawa K (2005) Open clamp structure in the clamp-loading complex visualized by electron microscopic image analysis. Proc Natl Acad Sci USA 102: 13795-13800
24. Obradovic Z, Peng K, Vucetic S, Radivojac P, Dunker AK (2005) Exploiting heterogeneous sequence properties improves prediction of protein disorder. Proteins 61: 176-182
25. Olson M, Wang Y, Elder R, Kaguni L (1995) Subunit structure of mitochondrial DNA polymerase from Drosophila embryos. J Biol Chem 270: 28932-28937
26. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera - A visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612
27. Pinz KG, Bogenhagen DF (2006) The influence of the DNA polymerase γ accessory subunit on base excision repair by the catalytic subunit. DNA Repair 5: 121-128
28. Scheres SHW, Gao H, Valle M, Herman GT, Eggermont PPB, Frank J, Carazo J-M (2007) Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization. Nat Methods 4: 27-29
29. Sickmeier M, Hamilton JA, LeGall T, Vacic V, Cortese MS, Tantos A, Szabo B, Tompa P, Chen J, Uversky VN, Obradovic Z, Dunker AK (2007) DisProt: the database of disordered proteins. Nucleic Acids Res 35: D786-D793
30. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink J, Rovio A, Bruder C, Bohlooly-Y M, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson N-G (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429: 417-423
31. Wall J, Hainfeld J, Simon M (1998) Scanning transmission electron microscopy of nuclear structures. Methods Cell Biol 53: 139-164
32. Yakubovskaya E, Chen Z, Carrodeguas JA, Kisker C, Bogenhagen DF (2006) Functional human mitochondrial DNA polymerase γ forms a heterotrimer. J Biol Chem 281: 374-382
33. Yang S, Yu X, Galkin VE, Egelman EH (2003) Issues of resolution and polymorphism in single-particle reconstruction. J Struct Biol 144: 162-171
34. Ye F, Carrodeguas JA, Bogenhagen DF (1996) The γ subfamily of DNA polymerases: cloning of a developmentally regulated cDNA encoding Xenopus laevis mitochondrial DNA polymerase γ. Nucleic Acids Res 24: 1481-1488
35. Zheng W, Khrapko K, Coller HA, Thilly WG, Copeland WC (2006) Origins of human mitochondrial point mutations as DNA polymerase γ-mediated errors. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 599: 11-20