Genetics, Vol 147, 1017-1024, Copyright © 1997

INVESTIGATIONS

A Role for REV3 in Mutagenesis During Double-Strand Break Repair in Saccharomyces cerevisiae

S. L. Holbeck and J. N. Strathern
Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, Maryland 21702-1201

Recombinational repair of double-strand breaks (DSBs), traditionally believed to be an error-free DNA repair pathway, was recently shown to increase the frequency of mutations in a nearby interval. The reversion rate of trp1 alleles (either nonsense or frameshift mutations) near an HO-endonuclease cleavage site is increased at least 100-fold among cells that have experienced an HO-mediated DSB. We report here that in strains deleted for rev3 this DSB-associated reversion of a nonsense mutation was greatly decreased. Thus REV3, which encodes a subunit of the translesion DNA polymerase {complex}, was responsible for the majority of these base substitution errors near a DSB. However, rev3 strains showed no decrease in HO-stimulated recombination, implying that another DNA polymerase also functioned in recombinational repair of a DSB. Reversion of trp1 frameshift alleles near a DSB was not reduced in rev3 strains, indicating that another polymerase could act during DSB repair to make these frameshift errors. Analysis of spontaneous reversion in haploid strains suggested that Rev3p had a greater role in making point mutations than in frameshift mutations.


This article has been cited by other articles:


Home page
 GeneticsHome page
E. Mito, J. V. Mokhnatkin, M. C. Steele, V. L. Buettner, S. S. Sommer, G. M. Manthey, and A. M. Bailis
Mutagenic and Recombinagenic Responses to Defective DNA Polymerase {delta} Are Facilitated by the Rev1 Protein in pol3-t Mutants of Saccharomyces cerevisiae
Genetics, August 1, 2008; 179(4): 1795 - 1806.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
K. Lee and S. E. Lee
Saccharomyces cerevisiae Sae2- and Tel1-Dependent Single-Strand DNA Formation at DNA Break Promotes Microhomology-Mediated End Joining
Genetics, August 1, 2007; 176(4): 2003 - 2014.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
X. Zhong, P. Garg, C. M. Stith, S. A. N. McElhinny, G. E. Kissling, P. M. J. Burgers, and T. A. Kunkel
The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with accessory proteins
Nucleic Acids Res., October 18, 2006; 34(17): 4731 - 4742.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. S. Waters and G. C. Walker
The critical mutagenic translesion DNA polymerase Rev1 is highly expressed during G2/M phase rather than S phase
PNAS, June 13, 2006; 103(24): 8971 - 8976.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. P. Wittschieben, S. C. Reshmi, S. M. Gollin, and R. D. Wood
Loss of DNA Polymerase {zeta} Causes Chromosomal Instability in Mammalian Cells
Cancer Res., January 1, 2006; 66(1): 134 - 142.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S.-W. Huang, R. Friedman, N. Yu, A. Yu, and W.-H. Li
How Strong Is the Mutagenicity of Recombination in Mammals?
Mol. Biol. Evol., March 1, 2005; 22(3): 426 - 431.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Wu, X. Lin, T. Okuda, and S. B. Howell
DNA Polymerase {zeta} Regulates Cisplatin Cytotoxicity, Mutagenicity, and The Rate of Development of Cisplatin Resistance
Cancer Res., November 1, 2004; 64(21): 8029 - 8035.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. Laurencon, C. M. Orme, H. K. Peters, C. L. Boulton, E. K. Vladar, S. A. Langley, E. P. Bakis, D. T. Harris, N. J. Harris, S. M. Wayson, et al.
A Large-Scale Screen for Mutagen-Sensitive Loci in Drosophila
Genetics, May 1, 2004; 167(1): 217 - 231.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Machida, K. T.-N. Cheng, V. M.-H. Sung, S. Shimodaira, K. L. Lindsay, A. M. Levine, M.-Y. Lai, and M. M. C. Lai
Hepatitis C virus induces a mutator phenotype: Enhanced mutations of immunoglobulin and protooncogenes
PNAS, March 23, 2004; 101(12): 4262 - 4267.
[Abstract] [Full Text] [PDF]

Home page
 Plant CellHome page
A. Sakamoto, V. T. T. Lan, Y. Hase, N. Shikazono, T. Matsunaga, and A. Tanaka
Disruption of the AtREV3 Gene Causes Hypersensitivity to Ultraviolet B Light and {gamma}-Rays in Arabidopsis: Implication of the Presence of a Translesion Synthesis Mechanism in Plants
PLANT CELL, September 1, 2003; 15(9): 2042 - 2057.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. G. Kozmin, Y. I. Pavlov, T. A. Kunkel, and E. Sage
Roles of Saccharomyces cerevisiae DNA polymerases Pol{eta} and Pol{zeta} in response to irradiation by simulated sunlight
Nucleic Acids Res., August 1, 2003; 31(15): 4541 - 4552.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
P. V. Shcherbakova, K. Bebenek, and T. A. Kunkel
Functions of Eukaryotic DNA Polymerases
Sci. Aging Knowl. Environ., February 26, 2003; 2003(8): re3 - 3.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. J. Rattray, B. K. Shafer, C. B. McGill, and J. N. Strathern
The Roles of REV3 and RAD57 in Double-Strand-Break-Repair-Induced Mutagenesis of Saccharomyces cerevisiae
Genetics, November 1, 2002; 162(3): 1063 - 1077.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
E. C. Friedberg, R. Wagner, and M. Radman
Specialized DNA Polymerases, Cellular Survival, and the Genesis of Mutations
Science, May 31, 2002; 296(5573): 1627 - 1630.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. P. H. Van Sloun, I. Varlet, E. Sonneveld, J. J. W. A. Boei, R. J. Romeijn, J. C. J. Eeken, and N. De Wind
Involvement of Mouse Rev3 in Tolerance of Endogenous and Exogenous DNA Damage
Mol. Cell. Biol., April 1, 2002; 22(7): 2159 - 2169.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
C. Pal, B. Papp, and L. D. Hurst
Does the Recombination Rate Affect the Efficiency of Purifying Selection? The Yeast Genome Provides a Partial Answer
Mol. Biol. Evol., December 1, 2001; 18(12): 2323 - 2326.
[Full Text] [PDF]

Home page
 GeneticsHome page
P. Cejka, V. Vondrejs, and Z. Storchova
Dissection of the Functions of the Saccharomyces cerevisiae RAD6 Postreplicative Repair Group in Mutagenesis and UV Sensitivity
Genetics, November 1, 2001; 159(3): 953 - 963.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
Y. I. Pavlov, P. V. Shcherbakova, and T. A. Kunkel
In Vivo Consequences of Putative Active Site Mutations in Yeast DNA Polymerases {alpha}, {epsilon}, {delta}, and {zeta}
Genetics, September 1, 2001; 159(1): 47 - 64.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. J. Bull, M.-J. Lombardo, and S. M. Rosenberg
Stationary-phase mutation in the bacterial chromosome: Recombination protein and DNA polymerase IV dependence
PNAS, July 17, 2001; 98(15): 8334 - 8341.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Diaz, L. K. Verkoczy, M. F. Flajnik, and N. R. Klinman
Decreased Frequency of Somatic Hypermutation and Impaired Affinity Maturation but Intact Germinal Center Formation in Mice Expressing Antisense RNA to DNA Polymerase {{zeta}}
J. Immunol., July 1, 2001; 167(1): 327 - 335.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. J. Rattray, C. B. McGill, B. K. Shafer, and J. N. Strathern
Fidelity of Mitotic Double-Strand-Break Repair in Saccharomyces cerevisiae: A Role for SAE2/COM1
Genetics, May 1, 2001; 158(1): 109 - 122.
[Abstract] [Full Text]

Home page
 GeneticsHome page
D. D. G. Gessler and S. Xu
Meiosis and the Evolution of Recombination at Low Mutation Rates
Genetics, September 1, 2000; 156(1): 449 - 456.
[Abstract] [Full Text]

Home page
 GeneticsHome page
H. J. Bull, G. J. McKenzie, P. J. Hastings, and S. M. Rosenberg
Evidence That Stationary-Phase Hypermutation in the Escherichia coli Chromosome Is Promoted by Recombination
Genetics, April 1, 2000; 154(4): 1427 - 1437.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
Y. Murakumo, T. Roth, H. Ishii, D. Rasio, S.-i. Numata, C. M. Croce, and R. Fishel
A Human REV7 Homolog That Interacts with the Polymerase zeta Catalytic Subunit hREV3 and the Spindle Assembly Checkpoint Protein hMAD2
J. Biol. Chem., February 11, 2000; 275(6): 4391 - 4397.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Esposito, G. Texido, U. A. K. Betz, H. Gu, W. Muller, U. Klein, and K. Rajewsky
Mice reconstituted with DNA polymerase beta -deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally
PNAS, February 1, 2000; 97(3): 1166 - 1171.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
F. Paques and J. E. Haber
Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae
Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 349 - 404.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
M.-J. LOMBARDO, J. TORKELSON, H. J. BULL, G. J. McKENZIE, and S. M. ROSENBERG
Mechanisms of Genome-Wide Hypermutation in Stationary Phase
Ann. N.Y. Acad. Sci., May 18, 1999; 870(1): 275 - 289.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
M. Diaz, J. Velez, M. Singh, J. Cerny, and M. F. Flajnik
Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation
Int. Immunol., May 1, 1999; 11(5): 825 - 833.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. Stambuk and M. Radman
Mechanism and Control of Interspecies Recombination in Escherichia coli. I. Mismatch Repair, Methylation, Recombination and Replication Functions
Genetics, October 1, 1998; 150(2): 533 - 542.
[Abstract] [Full Text]

Home page
 GeneticsHome page
C. B. McGill, S. L. Holbeck, and J. N. Strathern
The Chromosome Bias of Misincorporations During Double-Strand Break Repair Is Not Altered in Mismatch Repair–Defective Strains of Saccharomyces cerevisiae
Genetics, April 1, 1998; 148(4): 1525 - 1533.
[Abstract] [Full Text] [PDF]