Fidelity and Processivity of Saccharomyces cerevisiae DNA Polymerase η
Open accessAbstract
The yeast RAD30 gene functions in error-free replication of UV-damaged DNA, and RAD30 encodes a DNA polymerase, pol eta, that has the ability to efficiently and correctly replicate past a cis-syn-thymine-thymine dimer in template DNA. To better understand the role of pol eta in damage bypass, we examined its fidelity and processivity on nondamaged DNA templates. Steady-state kinetic analyses of deoxynucleotide incorporation indicate that pol eta has a low fidelity, misincorporating deoxynucleotides with a frequency of about 10(-2) to 10(-3). Also pol eta has a low processivity, incorporating only a few nucleotides before dissociating. We suggest that pol eta's low fidelity reflects a flexibility in its active site rendering it more tolerant of DNA damage, while its low processivity limits its activity to reduce errors.
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These multiplet mutations are likely the consequence of error-prone bypass polymerization during translesion synthesis and are consistent with processivity of bypass polymerases persisting for several nucleotides after the bypass-requiring blocking lesion.
“These multiplet mutations are likely the consequence of error-prone bypass polymerization during translesion synthesis and are consistent with the processivity of bypass polymerases persisting for several nucleotides after the bypass-requiring blocking lesion (39 -41).”
From Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency (2016) · cites this paper as [39]
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Cites
Enzyme structure and mechanism
Fersht, A. (1977) · Medical Entomology and Zoology · Cited by 2,875 · see citing works
Enzyme structure and mechanism
Elmore, D. T. (1978) · Endeavour · doi:10.1016/0160-9327(78)90081-9 · Cited by 2,723 · see citing works
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., & Hanaoka, F. (1999) · Nature · doi:10.1038/21447 · Cited by 1,292 · 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
Efficient Bypass of a Thymine-Thymine Dimer by Yeast DNA Polymerase, Polη
Johnson, R. E., Prakash, S., & Prakash, L. (1999) · Science · doi:10.1126/science.283.5404.1001 · Cited by 736 · see citing works
Self-citation<i>hRAD30</i> Mutations in the Variant Form of Xeroderma Pigmentosum
Johnson, R. E., Kondratick, C. M., Prakash, S., & Prakash, L. (1999) · Science · doi:10.1126/science.285.5425.263 · Cited by 732 · see citing works
Self-citationFIDELITY MECHANISMS IN DNA REPLICATION
Echols, H., & Goodman, M. F. (1991) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.60.070191.002401 · Cited by 712 · see citing works
Biochemical Basis of DNA Replication Fidelity
Goodman, M. F., Creighton, S., Bloom, L. B., Petruska, J., & Kunkel, T. A. (1993) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409239309086792 · Cited by 446 · see citing works
McDonald, J. P., Levine, A. S., & Woodgate, R. (1997) · Genetics · doi:10.1093/genetics/147.4.1557 · Cited by 314 · see citing works
Bailly, V., Lauder, S., Prakash, S., & Prakash, L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.23360 · Cited by 292 · see citing works
Self-citationKim, J., Patel, D., & Choi, B. (1995) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1995.tb05236.x · Cited by 240 · see citing works
Creighton, S., Bloom, L. B., & Goodman, M. F. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)62021-4 · Cited by 227 · see citing works
Wang, Y., Maher, V. M., Mitchell, D. L., & McCormick, J. J. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4276 · Cited by 161 · see citing works
The Fidelity of DNA Polymerase β during Distributive and Processive DNA Synthesis
Osheroff, W. P., Jung, H. K., Beard, W. A., Wilson, S. H., & Kunkel, T. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3642 · Cited by 141 · see citing works
Roush, A. A., Suarez, M., Friedberg, E. C., Radman, M., & Siede, W. (1998) · Molecular and General Genetics MGG · doi:10.1007/s004380050698 · Cited by 135 · see citing works
Fidelity of Escherichia coli DNA Polymerase III Holoenzyme
Bloom, L. B., Chen, X., Fygenson, D. K., Turner, J., O’Donnell, M. E., & Goodman, M. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.44.27919 · Cited by 123 · see citing works
Fidelity of mammalian DNA replication and replicative DNA polymerases
Thomas, D. C., Roberts, J. D., Sabatino, R. D., Myers, T. W., Tan, C. K., Downey, K. M., So, A. G., Bambara, R. A., & Kunkel, T. A. (1991) · Biochemistry · doi:10.1021/bi00115a003 · Cited by 121 · see citing works
DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding
Goodman, M. F., & Fygenson, D. K. (1998) · Genetics · doi:10.1093/genetics/148.4.1475 · Cited by 117 · see citing works
Kemmink, J., Boelens, R., Koning, T. M. G., MAREL, G. A. V. D., BOOM, J. H. V., & Kaptein, R. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.11.4645 · Cited by 111 · see citing works
Requirement of DNA Polymerase Activity of Yeast Rad30 Protein for Its Biological Function
Johnson, R. E., Prakash, S., & Prakash, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.23.15975 · Cited by 106 · see citing works
Self-citationWang, C.-I., & Taylor, J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.20.9072 · Cited by 102 · see citing works
Determination of pyrimidine dimer unwinding angle by measurement of DNA electrophoretic mobility
Ciarrocchi, G., & Pedrini, A. M. (1982) · Journal of Molecular Biology · doi:10.1016/0022-2836(82)90445-4 · Cited by 93 · see citing works
On the Processivity of Polymerasesa
von Hippel, P. H., Fairfield, F. R., & Dolejsi, M. K. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb52803.x · Cited by 85 · see citing works
Creighton, S., & Goodman, M. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.9.4759 · Cited by 73 · see citing works
Ultraviolet Hypermutablity of a Shuttle Vector Propagated in Xeroderma Pigmentosum Variant Cells
Waters, H. L., Seetharam, S., Seidman, M. M., & Kraemer, K. H. (1993) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12371686 · Cited by 65 · see citing works
[21] Methods of analyzing processivity
Bambara, R. A., Fay, P. J., & Mallaber, L. M. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)62023-0 · Cited by 51 · see citing works
Flagged first, then by citations
Research works printed but not linked: 23
- [1]1. McDonald, J.P. ∙ Levine, A.S. ∙ Woodgate, R. Genetics. 1997; 147:1557-1568 Crossref PubMed Google Scholar
- [2]2. Roush, A.A. ∙ Suarez, M. ∙ Friedberg, E.C. ... Mol. Gen. Genet. 1998; 257:686-692 Crossref Scopus (127) PubMed Google Scholar
- [3]3. Johnson, R.E. ∙ Prakash, S. ∙ Prakash, L. J. Biol. Chem. 1999; 274:15975-15977 Full Text Full Text (PDF) Scopus (108) PubMed Google Scholar
- [4]4. Johnson, R.E. ∙ Prakash, S. ∙ Prakash, L. Science. 1999; 283:1001-1004 Crossref Scopus (707) PubMed Google Scholar
- [5]5. Johnson, R.E. ∙ Kondratick, C.M. ∙ Prakash, S. ... Science. 1999; 285:263-265 Crossref Scopus (680) PubMed Google Scholar
- [6]6. Masutani, C. ∙ Kusumoto, R. ∙ Yamada, A. ... Nature. 1999; 399:700-704 Crossref Scopus (1178) PubMed Google Scholar
- [7]7. Echols, H. ∙ Goodman, M.F. Annu. Rev. Biochem. 1991; 60:477-511 Crossref Scopus (659) PubMed Google Scholar
- [8]8. Kemmink, J. ∙ Boelens, R. ∙ Koning, T. ... Nucleic Acids Res. 1987; 15:4645-4653 Crossref Scopus (105) PubMed Google Scholar
- [9]9. Kim, J.-K. ∙ Patel, D. ∙ Choi, B.-S. Photochem. Photobiol. 1995; 62:44-50 Crossref Scopus (210) PubMed Google Scholar
- [10]10. Ciarrocchi, G. ∙ Pedrini, A.M. J. Mol. Biol. 1982; 155:177-183 Crossref Scopus (77) PubMed Google Scholar
- [11]11. Wang, C.-I. ∙ Taylor, J.-S. Proc. Natl. Acad. Sci. U. S. A. 1991; 88:9072-9076 Crossref Scopus (98) PubMed Google Scholar
- [12]12. Goodman, M.F. ∙ Creighton, S. ∙ Bloom, L.B. ... Crit. Rev. Biochem. Mol. Biol. 1993; 28:83-126 Crossref Scopus (418) PubMed Google Scholar
- [13]13. Creighton, S. ∙ Bloom, L.B. ∙ Goodman, M.F. Methods Enzymol. 1995; 262:232-256 Crossref Scopus (229) PubMed Google Scholar
- [14]14. Bloom, L.B. ∙ Chen, X. ∙ Fygenson, D.K. ... J. Biol. Chem. 1997; 272:27919-27930 Full Text Full Text (PDF) Scopus (114) PubMed Google Scholar
- [15]15. von Hippel, P.H. ∙ Fairfield, F.R. ∙ Dolejsi, M.K. Ann. N. Y. Acad. Sci. 1994; 726:118-131 Crossref Scopus (77) PubMed Google Scholar
- [16]16. Goodman, M.F. ∙ Fygenson, D.K. Genetics. 1998; 148:1475-1482 Crossref PubMed Google Scholar
- [18]18. Bambara, R.A. ∙ Fay, P.J. ∙ Mallaber, L.M. Methods Enzymol. 1995; 262:270-280 Crossref Scopus (47) PubMed Google Scholar
- [19]19. Steitz, T.A. J. Biol. Chem. 1999; 274:17395-17398 Full Text Full Text (PDF) Scopus (730) PubMed Google Scholar
- [20]20. Creighton, S. ∙ Goodman, M.F. J. Biol. Chem. 1995; 270:4759-4774 Full Text Full Text (PDF) Scopus (64) PubMed Google Scholar
- [21]21. Thomas, D.C. ∙ Roberts, J.D. ∙ Sabatino, R.D. ... Biochemistry. 1991; 30:11751-11759 Crossref Scopus (105) PubMed Google Scholar
- [22]22. Osheroff, W.P. ∙ Jung, H.K. ∙ Beard, W.A. ... J. Biol. Chem. 1999; 274:3642-3650 Full Text Full Text (PDF) Scopus (139) PubMed Google Scholar
- [23]23. Wang, Y.-C. ∙ Maher, V.M. ∙ Mitchell, D.L. ... Mol. Cell. Biol. 1993; 13:4276-4283 Crossref Scopus (144) PubMed Google Scholar
- [24]24. Waters, H.L. ∙ Seetharam, S. ∙ Seidman, M.M. ... J. Investig. Dermatol. 1993; 101:744-748
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Goodman, M. F. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.083101.124707 · Cited by 727 · see citing works
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Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., & Prakash, L. (2000) · Nature · doi:10.1038/35023030 · Cited by 632 · see citing works
Self-citationEukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
Waters, L. S., Minesinger, B. K., Wiltrout, M. E., D'Souza, S., Woodruff, R. V., & Walker, G. C. (2009) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00034-08 · Cited by 591 · see citing works
Watanabe, K., Tateishi, S., Kawasuji, M., Tsurimoto, T., Inoue, H., & Yamaizumi, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600383 · Cited by 538 · see citing works
“PolZ synthesizes DNAwith a low fidelity, misincorporating nucleotides with a frequency of 10 2–10 3 (Washington et al, 1999).”
BackgroundRegulation of DNA cross-link repair by the Fanconi anemia/BRCA pathwayPreprint
Kim, H., & D’Andrea, A. D. (2012) · Genes & Development · doi:10.1101/gad.195248.112 · Cited by 510 · see citing works
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Masutani, C., Kusumoto, R., Iwai, S., & Hanaoka, F. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.3100 · Cited by 504 · see citing works
Low fidelity DNA synthesis by human DNA polymerase-η
Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., & Kunkel, T. A. (2000) · Nature · doi:10.1038/35010014 · Cited by 372 · see citing works
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Haracska, L., Yu, S.-L., Johnson, R. E., Prakash, L., & Prakash, S. (2000) · Nature Genetics · doi:10.1038/78169 · Cited by 349 · see citing works
Self-citationTranslesion DNA synthesis in eukaryotes: A one- or two-polymerase affair
Prakash, S., & Prakash, L. (2002) · Genes & Development · doi:10.1101/gad.1009802 · Cited by 344 · see citing works
“…to the high fidelity of replicative polymerases, Pol is a low-fidelity enzyme, and it misincorporates nucleotides with a frequency of ∼10−2 to 10−3 (Washington et al. 1999; Johnson et al. 2000c); in a subsequent study, human Pol was shown to be highly mutagenic in an in vitro DNA synthesis…”
BackgroundSelf-citationStructure of the Catalytic Core of S. cerevisiae DNA Polymerase η
Trincão, J., Johnson, R. E., Escalante, C. R., Prakash, S., Prakash, L., & Aggarwal, A. K. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00306-9 · Cited by 344 · see citing works
“; Washington et al., 1999, 2000; Johnson et diffract better and were used for the subsequent structure determial., 2000c; Matsuda et al., 2000).”
MethodSelf-citationTHE SOS RESPONSE: Recent Insights into umuDC -Dependent Mutagenesis and DNA Damage Tolerance
Sutton, M. D., Smith, B. T., Godoy, V. G., & Walker, G. C. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.479 · Cited by 318 · see citing works
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Backgroundpolι, a remarkably error-prone human DNA polymerase
Tissier, A., McDonald, J. P., Frank, E. G., & Woodgate, R. (2000) · Genes & Development · doi:10.1101/gad.14.13.1642 · Cited by 315 · see citing works
Translesion DNA Synthesis and Mutagenesis in Eukaryotes
Sale, J. E. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012708 · Cited by 282 · see citing works
“On undamaged DNA, however, Pol h is significantly error prone (Washington et al. 1999; Johnson et al. 2000c; Matsuda et al. 2000; Matsuda et al. 2001).”
BackgroundMolecular Mechanisms of DNA Damage and Repair: Progress in Plants
Tuteja, N., Singh, M. B., Misra, M. K., Bhalla, P. L., & Tuteja, R. (2001) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/20014091074219 · Cited by 272 · see citing works
“The DNA polymerase encoded by yeast RAD30 and human hRAD30A also bypasses a cis-syn thymine-thymine dimer efficiently and accurately (Johnson et al., 1999 a,b; Masutani et al., 1999; Washington et al., 1999; Johnson et al., 2000b, Washington et al., 2000).”
BackgroundRev1 Employs a Novel Mechanism of DNA Synthesis Using a Protein Template
Nair, D. T., Johnson, R. E., Prakash, L., Prakash, S., & Aggarwal, A. K. (2005) · Science · doi:10.1126/science.1116336 · Cited by 249 · see citing works
Self-citationPhysical and Functional Interactions of Human DNA Polymerase η with PCNA
Haracska, L., Johnson, R. E., Unk, I., Phillips, B., Hurwitz, J., Prakash, L., & Prakash, S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.21.7199-7206.2001 · Cited by 235 · see citing works
“Both yeast Pol and hPol are low-processivity enzymes, incorporating only a few nucleotides per DNA binding event (21, 38 ).”
BackgroundSelf-citationThe many faces of DNA polymerases: Strategies for mutagenesis and for mutational avoidance
Friedberg, E. C., Feaver, W. J., & Gerlach, V. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.120152397 · Cited by 222 · see citing works
Vaisman, A., Masutani, C., Hanaoka, F., & Chaney, S. G. (2000) · Biochemistry · doi:10.1021/bi000130k · Cited by 212 · see citing works
The Translesion DNA Polymerase ζ Plays a Major Role in Ig and bcl-6 Somatic Hypermutation
Zan, H., Komori, A., Li, Z., Cerutti, A., Schaffer, A., Flajnik, M. F., Diaz, M., & Casali, P. (2001) · Immunity · doi:10.1016/s1074-7613(01)00142-x · Cited by 204 · see citing works
“In spite of its highly distributive nature and intrinsic lack of proofreading capacity, pol η bypasses UV- and chemical-induced lesions by inserting deoxynucleotides mostly in an error-free fashion in yeast, mouse, and human cells, as it favors the intervention of exogenous 3′ → 5′ exonucleases (Johnson et al., 1999a,…”
BackgroundInfluentialPreferential Incorporation of G Opposite Template T by the Low-Fidelity Human DNA Polymerase ι
Zhang, Y., Yuan, F., Wu, X., & Wang, Z. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.19.7099-7108.2000 · Cited by 200 · see citing works
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MethodRole of DNA Polymerase η in the Bypass of a (6-4) TT Photoproduct
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Self-citationError-prone lesion bypass by human DNA polymerase eta
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Self-citationMcDonald, J. P., Frank, E. G., Plosky, B. S., Rogozin, I. B., Masutani, C., Hanaoka, F., Woodgate, R., & Gearhart, P. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030767 · Cited by 172 · see citing works
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BackgroundSelf-citationRecent developments in the optimization of thermostable DNA polymerases for efficient applications
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BackgroundSelf-citationKokoska, R. J., McCulloch, S. D., & Kunkel, T. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308515200 · Cited by 126 · see citing works
Barbour, L., & Xiao, W. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.014 · Cited by 125 · see citing works
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Fiala, K. A., & Suo, Z. (2004) · Biochemistry · doi:10.1021/bi0357457 · Cited by 115 · see citing works
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“Pol, which exhibit nearly similar efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases (17, 19, 44 ), Pol is unusual in that the efficiency and fidelity of nucleotide incorporation by this polymerase is dependent on the identity of the template base.”
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“The total buried surface area between the to 10 3 for Pol (Johnson et al. 2000a, 2000c; Washington et al. 1999).”
BackgroundSelf-citationBerdis, A. J. (2009) · Chemical Reviews · doi:10.1021/cr800530b · Cited by 113 · see citing works
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Parker, J. L., Bielen, A. B., Đikić, I., & Ulrich, H. D. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl1102 · Cited by 104 · see citing works
Regulated Proteolysis of DNA Polymerase η during the DNA-Damage Response in C. elegans
Kim, S.-H., & Michael, W. M. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.11.016 · Cited by 99 · see citing works
“…polymerase after TLS. Current models for TLS suggest that post-TLS exchange occurs because pol h, which exhibits low processivity in vitro (Washington et al., 1999; McCulloch et al., 2004, 2007), simply disassociates from the template after TLS, and this allows the replicative polymerase…”
BackgroundTranslesion synthesis by the UmuC family of DNA polymerases
Wang, Z. (2001) · Mutation Research/DNA Repair · doi:10.1016/s0921-8777(01)00089-1 · Cited by 99 · see citing works
Guo, D. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.13.2875 · Cited by 98 · see citing works
“Kinetic analysis of primer extension by yeast Polζ was performed using a previously described method (30,40,41).”
MethodBergoglio, V., Canitrot, Y., Hogarth, L., Minto, L., Howell, S. B., Cazaux, C., & Hoffmann, J. (2001) · Oncogene · doi:10.1038/sj.onc.1204743 · Cited by 92 · see citing works
“New cellular error-prone DNA polymerases have been recently described (Matsuda et al., 2000; Washington et al., 1999) which belong to the superfamily of DNA polymerases that are able to bypass lesions in DNA (Woodgate, 1999).”
BackgroundCoping with replication ‘train wrecks’ in Escherichia coli using Pol V, Pol II and RecA proteins
Goodman, M. F. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01564-4 · Cited by 107 · see citing works
Variations on a theme: Eukaryotic Y-family DNA polymerases
Washington, M. T., Carlson, K. D., Freudenthal, B., & Pryor, J. M. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.07.004 · Cited by 87 · see citing works
“Steady state kinetic studies as well as other complementary approaches have shown that purified yeast andmammalianpolη synthesizeDNAwith a low fidelity with error frequencies ranging from 10 to 10 [30,31,42–44].”
BackgroundSelf-citationReconstitution of translesion synthesis reveals a mechanism of eukaryotic DNA replication restart
Guilliam, T. A., & Yeeles, J. T. P. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0418-4 · Cited by 81 · see citing works
Xeroderma pigmentosum genes: Functions inside and outside DNA repair
Sugasawa, K. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm282 · Cited by 83 · see citing works
“This seems to be regulated at several levels, including low processivity of the enzyme itself (150, 164), altered binding affinities for different template-primer structures (165), and interaction with a monoubiquitylated PCNA clamp (166, 167).”
BackgroundChan, K., Resnick, M. A., & Gordenin, D. A. (2013) · DNA repair · doi:10.1016/j.dnarep.2013.07.008 · Cited by 81 · see citing works
Kozmin, S. G. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg489 · Cited by 78 · see citing works
Eoff, R. L., Irimia, A., Angel, K. C., Egli, M., & Guengerich, F. P. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702290200 · Cited by 77 · see citing works
Mechanism of nucleotide incorporation opposite a thymine-thymine dimer by yeast DNA polymerase η
Washington, M. T., Prakash, L., & Prakash, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2134223100 · Cited by 76 · see citing works
Self-citationRequirement of Watson-Crick Hydrogen Bonding for DNA Synthesis by Yeast DNA Polymerase η
Washington, M. T., Helquist, S. A., Kool, E. T., Prakash, L., & Prakash, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.14.5107-5112.2003 · Cited by 75 · see citing works
“This is because for certain base pairs, Pol preferentially incorporates the correct nucleotide several thousandfold more efficiently than the incorrect nucleotide ( 45 ) and because Pol requires minor-groove interactions between the protein and the incoming nucleotide substrate (47).”
BackgroundInfluentialSelf-citationMadia, F., Wei, M., Yuan, V., Hu, J. H., Gattazzo, C., Pham, P., Goodman, M. F., & Longo, V. D. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200906011 · Cited by 73 · see citing works
“…show that age-dependent mutagenesis was reduced in cells lacking either REV3 or REV7, the two subunits of Pol polymerase, but was increased in mutants lacking RAD30, which is regarded as an error-free DNA damage bypass enzyme (Johnson et al., 1999; Washington et al., 1999; Prakash et al., 2000).”
BackgroundInfluentialAccuracy of lesion bypass by yeast and human DNA polymerase η
Washington, M. T., Johnson, R. E., Prakash, L., & Prakash, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121007298 · Cited by 71 · see citing works
Self-citationReconstitution of DNA repair synthesis in vitro and the role of polymerase and helicase activities
Šebesta, M., Burkovics, P., Haracska, L., & Krejčí, L. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.03.003 · Cited by 69 · see citing works
DNA polymerase iota and related Rad30–like enzymes
McDonald, J. P., Tissier, A., Frank, E. G., Iwai, S., Hanaoka, F., & Woodgate, R. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2000.0748 · Cited by 68 · see citing works
Helix–hairpin–helix motifs confer salt resistance and processivity on chimeric DNA polymerases
Pavlov, A. R., Belova, G. I., Kozyavkin, S. A., & Slesarev, A. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202127199 · Cited by 66 · see citing works
Carlson, K. D., & Washington, M. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.6.2169-2176.2005 · Cited by 70 · see citing works
“In Saccharomyces cerevisiae, disruption of the RAD30 gene encoding Pol results in increased sensitivity to UV irradiation and an increase in the number of UVinduced mutations ( 21 , 30, 37).”
BackgroundInfluentialSelf-citationProcessivity of Ribozyme-Catalyzed RNA Polymerization
Lawrence, M. S., & Bartel, D. P. (2003) · Biochemistry · doi:10.1021/bi034228l · Cited by 62 · see citing works
“9, placing it among lowprocessivity proteinaceous polymerases such as yeast polymeraseη (12).”
Enhanced Genetic Integrity in Mouse Germ Cells1
Murphey, P., McLean, D. J., McMahan, C. A., Walter, C. A., & McCarrey, J. R. (2012) · Biology of Reproduction · doi:10.1095/biolreprod.112.103481 · Cited by 57 · see citing works
Franklin, A., Milburn, P. J., Blanden, R. V., & Steele, E. J. (2004) · Immunology and Cell Biology · doi:10.1046/j.0818-9641.2004.01221.x · Cited by 56 · see citing works
Washington, M. T., Johnson, R. E., Prakash, L., & Prakash, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.24.2.936-943.2004 · Cited by 55 · see citing works
“Pol from both yeast and humans synthesizes DNA with a low fidelity, misincorporating nucleotides with frequencies of 10 2 to 10 3 (11, 14, 19).”
BackgroundSelf-citationEvidence for a Watson-Crick Hydrogen Bonding Requirement in DNA Synthesis by Human DNA Polymerase κ
Wolfle, W. T., Washington, M. T., Kool, E. T., Spratt, T. E., Helquist, S. A., Prakash, L., & Prakash, S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.7137-7143.2005 · Cited by 55 · see citing works
“For example, both yeast and human Pol misincorporate nucleotides with a frequency of 102 to 103, and both of these enzymes replicate through a cis-syn TT dimer by inserting two A’s opposite the two T’s of the dimer with the same efficiency and fidelity as opposite the undamaged T’s (12, 40, 41 , 43).”
BackgroundSelf-citationWhy Cockayne syndrome patients do not get cancer despite their DNA repair deficiency
Reid-Bayliss, K. S., Arron, S. T., Loeb, L. A., Bezrookove, V., & Cleaver, J. E. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610020113 · Cited by 55 · see citing works
Mismatch Extension Ability of Yeast and Human DNA Polymerase η
Washington, M. T., Johnson, R. E., Prakash, S., & Prakash, L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009049200 · Cited by 54 · see citing works
Self-citationBellows, A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg811 · Cited by 53 · see citing works
Lehmann, A. R. (2000) · Gene · doi:10.1016/s0378-1119(00)00250-x · Cited by 52 · see citing works
Involvement of DNA polymerase β in DNA replication and mutagenic consequences
Servant, L., Bieth, A., Hayakawa, H., Cazaux, C., & Hoffmann, J. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5307 · Cited by 53 · see citing works
Skoneczna, A., McIntyre, J., Skoneczny, M., Policińska, Z., & Śledziewska-Gójska, E. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.11.093 · Cited by 53 · see citing works
Monitoring Processivity and Length Control of a Carbohydrate Polymerase
Levengood, M. R., Splain, R. A., & Kiessling, L. L. (2011) · Journal of the American Chemical Society · doi:10.1021/ja204448t · Cited by 51 · see citing works
Seo, K. Y., Nagalingam, A., Miri, S., Yin, J., Chandani, S., Kolbanovskiy, A., Shastry, A., & Loechler, E. L. (2006) · DNA repair · doi:10.1016/j.dnarep.2005.12.009 · Cited by 51 · see citing works
Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion
Ober, M. S., Müller, H., Pieck, C., Gierlich, J., & Carell, T. (2005) · Journal of the American Chemical Society · doi:10.1021/ja0549188 · Cited by 49 · see citing works
Pavlov, Y. I., Nguyen, D., & Kunkel, T. A. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00131-2 · Cited by 48 · see citing works
Degradation or Maintenance: Actions of the Ubiquitin System on Eukaryotic Chromatin
Ulrich, H. D. (2002) · Eukaryotic Cell · doi:10.1128/ec.1.1.1-10.2002 · Cited by 47 · see citing works
“However, the overall fidelity of Pol on nondamaged templates is much lower than that of replicative polymerases (128).”
BackgroundĆejka, P., Vondrejs, V., & Štorchová, Z. (2001) · Genetics · doi:10.1093/genetics/159.3.953 · Cited by 46 · see citing works
Acidic Residues Critical for the Activity and Biological Function of Yeast DNA Polymerase η
Kondratick, C. M., Washington, M. T., Prakash, S., & Prakash, L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.6.2018-2025.2001 · Cited by 46 · see citing works
“relative insensitivity of Polh to geometric distortions in DNA may derive from a flexible active site able to conform to distortions in Watson-Crick geometry (8, 17, 31, 32 ).”
BackgroundSelf-citationY-Family Polymerase Conformation Is a Major Determinant of Fidelity and Translesion Specificity
Wilson, R. C., Jackson, M. A., & Pata, J. D. (2012) · Structure · doi:10.1016/j.str.2012.11.005 · Cited by 45 · see citing works
“The importance of these polymerases became apparent when the variant form of xeroderma pigmentosum (XPV) was found to be caused by a lack of polymerase (pol) eta, which was shown to have the ability to bypass cis-syn cyclopyrimidine dimers (CPD) accurately (McDonald et al., 1999; Washington et al., 1999).”
BackgroundWashington, M. T., Johnson, R. E., Prakash, L., & Prakash, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8316-8322.2003 · Cited by 45 · see citing works
“Pol can also efficiently replicate through other DNA lesions, such as 8-oxoguanine and O6-methylguanine (4, 5). We previously suggested (as determined on the basis of the proficient ability of Pol to replicate through distorting DNA lesions) that Pol possesses an active site that is remarkably tolerant of geometric di…”
BackgroundInfluentialSelf-citationWolfle, W. T., Johnson, R. E., Minko, I. G., Lloyd, R. S., Prakash, S., & Prakash, L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.19.8748-8754.2005 · Cited by 45 · see citing works
“Similar to high-fidelity replicative polymerases, Pols and incorporate nucleotides opposite the four template bases with nearly equivalent efficiencies and fidelities (6, 8, 23), while Pol incorporates nucleotides opposite the four template bases with very different efficiencies and fidelities (2, 7, 19, 21).”
BackgroundSelf-citationGarcía‐Ortiz, M. V., Ariza, R. R., Hoffman, P. D., Hays, J. B., & Roldán‐Arjona, T. (2004) · The Plant Journal · doi:10.1111/j.1365-313x.2004.02112.x · Cited by 45 · see citing works
Song, L., Chaudhuri, M. M., Knopf, C. W., & Parris, D. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309848200 · Cited by 43 · see citing works
Human PrimPol mutation associated with high myopia has a DNA replication defect
Keen, B. A., Bailey, L. J., Jóźwiakowski, S. K., & Doherty, A. J. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku879 · Cited by 43 · see citing works
“The PrimPol variants were analysed for processivity as described previously (16).”
MethodAbdulovic, A. L., & Jinks-Robertson, S. (2005) · Genetics · doi:10.1534/genetics.105.052480 · Cited by 43 · see citing works
“In spite of its original designation as an error-free TLS polymerase, Polh has very low fidelity when copying undamaged DNA templates (Washington et al.1999) and is important for UV-induced mutagenesis in at least some yeast assays (Zhang and Siede 2002).”
BackgroundHaracska, L., Prakash, L., & Prakash, S. (2003) · Genes & Development · doi:10.1101/gad.1146103 · Cited by 41 · see citing works
“Steady-state kinetic analyses have indicated that Pol and Pol misincorporate nucleotides with a frequency of ∼10−2 to 10−3 and ∼10−3 to 10−4, respectively (Washington et al. 1999; Johnson et al. 2000a,c).”
BackgroundSelf-citationMutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι
Ishikawa, T., Uematsu, N., Mizukoshi, T., Iwai, S., Iwasaki, H., Masutani, C., Hanaoka, F., Ueda, R., Ohmori, H., & Todo, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009822200 · Cited by 37 · see citing works
Zhang, H. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.5.1262 · Cited by 38 · see citing works
Minko, I. G., Washington, M. T., Prakash, L., Prakash, S., & Lloyd, R. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007867200 · Cited by 37 · see citing works
Self-citationDieckman, L. M., Johnson, R. E., Prakash, S., & Washington, M. (2010) · Biochemistry · doi:10.1021/bi100556m · Cited by 37 · see citing works
“translesion synthesis polymerases such as pol ζ [45], pol η [46,47], pol κ [48], and pol ι [45,49,50], which have error rates as high as 101 for pol ι and as low as 10−4 for pol ζ and pol κ.”
BackgroundSelf-citationWashington, M. T., Wolfle, W. T., Spratt, T. E., Prakash, L., & Prakash, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0837578100 · Cited by 35 · see citing works
Self-citationThe Y-Family DNA Polymerase Dpo4 Uses a Template Slippage Mechanism To Create Single-Base Deletions
Wu, Y., Wilson, R. C., & Pata, J. D. (2011) · Journal of Bacteriology · doi:10.1128/jb.00012-11 · Cited by 34 · see citing works
“The Y-family of DNA polymerases was defined in 2001 (21), following the discovery that the gene responsible for the variant form of xeroderma pigmentosum encodes polymerase (Pol) eta, the seventh human polymerase identified (19, 30).”
BackgroundRepair of Oxidative DNA Damage in Saccharomyces cerevisiae
Chalissery, J., Jalal, D., Natour, Z. A., & Hassan, A. H. (2017) · DNA repair · doi:10.1016/j.dnarep.2016.12.010 · Cited by 34 · see citing works
Regulatory Role of Ubiquitin in Eukaryotic DNA Translesion Synthesis
Yang, K., Weinacht, C. P., & Zhuang, Z. (2013) · Biochemistry · doi:10.1021/bi400194r · Cited by 33 · see citing works
- Authors
- Washington, M. T., Johnson, R. E., Prakash, S., & Prakash, L.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Prakash, Louise
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 274
- Issue
- 52
- Pages
- 36835-36838
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2107896468
- Cited by
- 181
- References
- 26
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm019261-30)
- National Institute of General Medical Sciences (GM-19261)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA polymerase eta, UV-damaged DNA, translesion synthesis, polymerase fidelity, polymerase processivity, active site flexibility, Saccharomyces cerevisiae
- MeSH terms
- DNA Polymerase iota, Y-Family DNA Polymerases, DNA Damage, DNA-Directed DNA Polymerase, DNA Replication, Kinetics, Mutation, Saccharomyces cerevisiae
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