Previous Article | Next Article 
Mol Cell Biol, May 1998, p. 2779-2788, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Destabilization of Yeast Micro- and Minisatellite DNA Sequences
by Mutations Affecting a Nuclease Involved in Okazaki Fragment
Processing (rad27) and DNA Polymerase
(pol3-t)
Robert J.
Kokoska,1
Lela
Stefanovic,1
Hiep T.
Tran,2
Michael A.
Resnick,2
Dmitry A.
Gordenin,2,3 and
Thomas D.
Petes1,*
Department of Biology and Curriculum in
Genetics and Molecular Biology, University of North Carolina,
Chapel Hill, North Carolina 275991;
Laboratory of Molecular Genetics, National Institute of
Environmental Health Sciences, Research Triangle Park, North Carolina
277092; and
Department of Genetics,
St. Petersburg State University, St. Petersburg 199034, Russia3
Received 17 October 1997/Returned for modification 16 December
1997/Accepted 19 February 1998
We examined the effects of mutations in the Saccharomyces
cerevisiae RAD27 (encoding a nuclease involved in the processing of Okazaki fragments) and POL3 (encoding DNA polymerase
) genes on the stability of a minisatellite sequence (20-bp repeats)
and microsatellites (1- to 8-bp repeat units). Both the
rad27 and pol3-t mutations destabilized both
classes of repeats, although the types of tract alterations observed in
the two mutant strains were different. The tract alterations observed
in rad27 strains were primarily additions, and those
observed in pol3-t strains were primarily deletions.
Measurements of the rates of repetitive tract alterations in strains
with both rad27 and pol3-t indicated that the
stimulation of microsatellite instability by rad27 was reduced by the effects of the pol3-t mutation. We also
found that rad27 and pol3-01 (an allele
carrying a mutation in the "proofreading" exonuclease domain of DNA
polymerase
) mutations were synthetically lethal.
*
Corresponding author. Mailing address: Department of
Biology and Curriculum in Genetics and Molecular Biology, University of
North Carolina, Chapel Hill, NC 27599-3280. Phone: (919) 962-1330. Fax:
(919) 962-1625. E-mail: tompetes{at}email.unc.edu.
Mol Cell Biol, May 1998, p. 2779-2788, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Karanja, K. K., Livingston, D. M.
(2009). C-Terminal Flap Endonuclease (rad27) Mutations: Lethal Interactions With a DNA Ligase I Mutation (cdc9-p) and Suppression by Proliferating Cell Nuclear Antigen (POL30) in Saccharomyces cerevisiae. Genetics
183: 63-78
[Abstract]
[Full Text]
-
Richard, G.-F., Kerrest, A., Dujon, B.
(2008). Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes. Microbiol. Mol. Biol. Rev.
72: 686-727
[Abstract]
[Full Text]
-
Mito, E., Mokhnatkin, J. V., Steele, M. C., Buettner, V. L., Sommer, S. S., Manthey, G. M., Bailis, A. M.
(2008). Mutagenic and Recombinagenic Responses to Defective DNA Polymerase {delta} Are Facilitated by the Rev1 Protein in pol3-t Mutants of Saccharomyces cerevisiae. Genetics
179: 1795-1806
[Abstract]
[Full Text]
-
Navarro, M. S., Bi, L., Bailis, A. M.
(2007). A Mutant Allele of the Transcription Factor IIH Helicase Gene, RAD3, Promotes Loss of Heterozygosity in Response to a DNA Replication Defect in Saccharomyces cerevisiae. Genetics
176: 1391-1402
[Abstract]
[Full Text]
-
Singh, P., Zheng, L., Chavez, V., Qiu, J., Shen, B.
(2007). Concerted Action of Exonuclease and Gap-dependent Endonuclease Activities of FEN-1 Contributes to the Resolution of Triplet Repeat Sequences (CTG)n- and (GAA)n-derived Secondary Structures Formed during Maturation of Okazaki Fragments. J. Biol. Chem.
282: 3465-3477
[Abstract]
[Full Text]
-
Dixon, K., Bayliss, C. D., Makepeace, K., Moxon, E. R., Hood, D. W.
(2007). Identification of the Functional Initiation Codons of a Phase-Variable Gene of Haemophilus influenzae, lic2A, with the Potential for Differential Expression. J. Bacteriol.
189: 511-521
[Abstract]
[Full Text]
-
Rossi, M. L., Bambara, R. A.
(2006). Reconstituted Okazaki Fragment Processing Indicates Two Pathways of Primer Removal. J. Biol. Chem.
281: 26051-26061
[Abstract]
[Full Text]
-
Lopes, J., Ribeyre, C., Nicolas, A.
(2006). Complex Minisatellite Rearrangements Generated in the Total or Partial Absence of Rad27/hFEN1 Activity Occur in a Single Generation and Are Rad51 and Rad52 Dependent.. Mol. Cell. Biol.
26: 6675-6689
[Abstract]
[Full Text]
-
Stone, J. E., Petes, T. D.
(2006). Analysis of the Proteins Involved in the in Vivo Repair of Base-Base Mismatches and Four-Base Loops Formed During Meiotic Recombination in the Yeast Saccharomyces cerevisiae. Genetics
173: 1223-1239
[Abstract]
[Full Text]
-
Farah, J. A., Cromie, G., Davis, L., Steiner, W. W., Smith, G. R.
(2005). Activation of an Alternative, Rec12 (Spo11)-Independent Pathway of Fission Yeast Meiotic Recombination in the Absence of a DNA Flap Endonuclease. Genetics
171: 1499-1511
[Abstract]
[Full Text]
-
Refsland, E. W., Livingston, D. M.
(2005). Interactions Among DNA Ligase I, the Flap Endonuclease and Proliferating Cell Nuclear Antigen in the Expansion and Contraction of CAG Repeat Tracts in Yeast. Genetics
171: 923-934
[Abstract]
[Full Text]
-
Zaleski, P., Wojciechowski, M., Piekarowicz, A.
(2005). The role of Dam methylation in phase variation of Haemophilus influenzae genes involved in defence against phage infection. Microbiology
151: 3361-3369
[Abstract]
[Full Text]
-
Sweetman, W. A., Moxon, E. R., Bayliss, C. D.
(2005). Induction of the SOS regulon of Haemophilus influenzae does not affect phase variation rates at tetranucleotide or dinucleotide repeats. Microbiology
151: 2751-2763
[Abstract]
[Full Text]
-
Wells, R. D., Dere, R., Hebert, M. L., Napierala, M., Son, L. S.
(2005). Advances in mechanisms of genetic instability related to hereditary neurological diseases. Nucleic Acids Res
33: 3785-3798
[Abstract]
[Full Text]
-
Jensen, L. E., Jauert, P. A., Kirkpatrick, D. T.
(2005). The Large Loop Repair and Mismatch Repair Pathways of Saccharomyces cerevisiae Act on Distinct Substrates During Meiosis. Genetics
170: 1033-1043
[Abstract]
[Full Text]
-
Li, L., Murphy, K. M., Kanevets, U., Reha-Krantz, L. J.
(2005). Sensitivity to Phosphonoacetic Acid: A New Phenotype to Probe DNA Polymerase {delta} in Saccharomyces cerevisiae. Genetics
170: 569-580
[Abstract]
[Full Text]
-
Wang, W., Bambara, R. A.
(2005). Human Bloom Protein Stimulates Flap Endonuclease 1 Activity by Resolving DNA Secondary Structure. J. Biol. Chem.
280: 5391-5399
[Abstract]
[Full Text]
-
Bayliss, C. D., Sweetman, W. A., Moxon, E. R.
(2005). Destabilization of tetranucleotide repeats in Haemophilus influenzae mutants lacking RnaseHI or the Klenow domain of PolI. Nucleic Acids Res
33: 400-408
[Abstract]
[Full Text]
-
Jin, Y. H., Garg, P., Stith, C. M. W., Al-Refai, H., Sterling, J. F., Murray, L. J. W., Kunkel, T. A., Resnick, M. A., Burgers, P. M., Gordenin, D. A.
(2005). The Multiple Biological Roles of the 3'->5' Exonuclease of Saccharomyces cerevisiae DNA Polymerase {delta} Require Switching between the Polymerase and Exonuclease Domains. Mol. Cell. Biol.
25: 461-471
[Abstract]
[Full Text]
-
Bayliss, C. D., Sweetman, W. A., Moxon, E. R.
(2004). Mutations in Haemophilus influenzae Mismatch Repair Genes Increase Mutation Rates of Dinucleotide Repeat Tracts but Not Dinucleotide Repeat-Driven Pilin Phase Variation Rates. J. Bacteriol.
186: 2928-2935
[Abstract]
[Full Text]
-
Liu, Y., Zhang, H., Veeraraghavan, J., Bambara, R. A., Freudenreich, C. H.
(2004). Saccharomyces cerevisiae Flap Endonuclease 1 Uses Flap Equilibration To Maintain Triplet Repeat Stability. Mol. Cell. Biol.
24: 4049-4064
[Abstract]
[Full Text]
-
Sharma, S., Otterlei, M., Sommers, J. A., Driscoll, H. C., Dianov, G. L., Kao, H.-I, Bambara, R. A., Brosh, R. M. Jr.
(2004). WRN Helicase and FEN-1 Form a Complex upon Replication Arrest and Together Process Branchmigrating DNA Structures Associated with the Replication Fork. Mol. Biol. Cell
15: 734-750
[Abstract]
[Full Text]
-
Callahan, J. L., Andrews, K. J., Zakian, V. A., Freudenreich, C. H.
(2003). Mutations in Yeast Replication Proteins That Increase CAG/CTG Expansions Also Increase Repeat Fragility. Mol. Cell. Biol.
23: 7849-7860
[Abstract]
[Full Text]
-
Gutierrez, P. J. A., Wang, T. S.-F.
(2003). Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1. Genetics
165: 65-81
[Abstract]
[Full Text]
-
Yamada, N.A., Castro, A., Farber, R.A.
(2003). Variation in the extent of microsatellite instability in human cell lines with defects in different mismatch repair genes. Mutagenesis
18: 277-282
[Abstract]
[Full Text]
-
Galli, A., Cervelli, T., Schiestl, R. H.
(2003). Characterization of the Hyperrecombination Phenotype of the pol3-t Mutation of Saccharomyces cerevisiae. Genetics
164: 65-79
[Abstract]
[Full Text]
-
Ayyagari, R., Gomes, X. V., Gordenin, D. A., Burgers, P. M. J.
(2003). Okazaki Fragment Maturation in Yeast. I. DISTRIBUTION OF FUNCTIONS BETWEEN FEN1 AND DNA2. J. Biol. Chem.
278: 1618-1625
[Abstract]
[Full Text]
-
Parenteau, J., Wellinger, R. J.
(2002). Differential Processing of Leading- and Lagging-Strand Ends at Saccharomyces cerevisiae Telomeres Revealed by the Absence of Rad27p Nuclease. Genetics
162: 1583-1594
[Abstract]
[Full Text]
-
Bhattacharyya, S., Rolfsmeier, M. L., Dixon, M. J., Wagoner, K., Lahue, R. S.
(2002). Identification of RTG2 as a Modifier Gene for CTG{middle dot}CAG Repeat Instability in Saccharomyces cerevisiae. Genetics
162: 579-589
[Abstract]
[Full Text]
-
Kucherlapati, M., Yang, K., Kuraguchi, M., Zhao, J., Lia, M., Heyer, J., Kane, M. F., Fan, K., Russell, R., Brown, A. M. C., Kneitz, B., Edelmann, W., Kolodner, R. D., Lipkin, M., Kucherlapati, R.
(2002). Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression. Proc. Natl. Acad. Sci. USA
99: 9924-9929
[Abstract]
[Full Text]
-
Henricksen, L. A., Veeraraghavan, J., Chafin, D. R., Bambara, R. A.
(2002). DNA Ligase I Competes with FEN1 to Expand Repetitive DNA Sequences in Vitro. J. Biol. Chem.
277: 22361-22369
[Abstract]
[Full Text]
-
Genschel, J., Bazemore, L. R., Modrich, P.
(2002). Human Exonuclease I Is Required for 5' and 3' Mismatch Repair. J. Biol. Chem.
277: 13302-13311
[Abstract]
[Full Text]
-
Huang, M.-E., Rio, A.-G., Galibert, M.-D., Galibert, F.
(2002). Pol32, a Subunit of Saccharomyces cerevisiae DNA Polymerase {delta}, Suppresses Genomic Deletions and Is Involved in the Mutagenic Bypass Pathway. Genetics
160: 1409-1422
[Abstract]
[Full Text]
-
Nagata, Y., Mashimo, K., Kawata, M., Yamamoto, K.
(2002). The Roles of Klenow Processing and Flap Processing Activities of DNA Polymerase I in Chromosome Instability in Escherichia coli K12 Strains. Genetics
160: 13-23
[Abstract]
[Full Text]
-
Corrette-Bennett, S. E., Mohlman, N. L., Rosado, Z., Miret, J. J., Hess, P. M., Parker, B. O., Lahue, R. S.
(2001). Efficient repair of large DNA loops in Saccharomyces cerevisiae. Nucleic Acids Res
29: 4134-4143
[Abstract]
[Full Text]
-
Pavlov, Y. I., Shcherbakova, P. V., Kunkel, T. A.
(2001). In Vivo Consequences of Putative Active Site Mutations in Yeast DNA Polymerases {alpha}, {epsilon}, {delta}, and {zeta}. Genetics
159: 47-64
[Abstract]
[Full Text]
-
Xie, Y., Liu, Y., Argueso, J. L., Henricksen, L. A., Kao, H.-I, Bambara, R. A., Alani, E.
(2001). Identification of rad27 Mutations That Confer Differential Defects in Mutation Avoidance, Repeat Tract Instability, and Flap Cleavage. Mol. Cell. Biol.
21: 4889-4899
[Abstract]
[Full Text]
-
Debrauwere, H., Loeillet, S., Lin, W., Lopes, J., Nicolas, A.
(2001). Links between replication and recombination in Saccharomyces cerevisiae: A hypersensitive requirement for homologous recombination in the absence of Rad27 activity. Proc. Natl. Acad. Sci. USA
98: 8263-8269
[Abstract]
[Full Text]
-
Jin, Y. H., Obert, R., Burgers, P. M. J., Kunkel, T. A., Resnick, M. A., Gordenin, D. A.
(2001). The 3'right-arrow5' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability. Proc. Natl. Acad. Sci. USA
10.1073/pnas.091095198v1
[Abstract]
[Full Text]
-
Negritto, M. C., Qiu, J., Ratay, D. O., Shen, B., Bailis, A. M.
(2001). Novel Function of Rad27 (FEN-1) in Restricting Short-Sequence Recombination. Mol. Cell. Biol.
21: 2349-2358
[Abstract]
[Full Text]
-
Kokoska, R. J., Stefanovic, L., DeMai, J., Petes, T. D.
(2000). Increased Rates of Genomic Deletions Generated by Mutations in the Yeast Gene Encoding DNA Polymerase delta or by Decreases in the Cellular Levels of DNA Polymerase delta. Mol. Cell. Biol.
20: 7490-7504
[Abstract]
[Full Text]
-
Chen, J. Z., Qiu, J., Shen, B., Holmquist, G. P.
(2000). Mutational spectrum analysis of RNase H(35) deficient Saccharomyces cerevisiae using fluorescence-based directed termination PCR. Nucleic Acids Res
28: 3649-3656
[Abstract]
[Full Text]
-
Bishop, A. J. R., Louis, E. J., Borts, R. H.
(2000). Minisatellite Variants Generated in Yeast Meiosis Involve DNA Removal During Gene Conversion. Genetics
156: 7-20
[Abstract]
[Full Text]
-
Kirchner, J. M., Tran, H., Resnick, M. A.
(2000). A DNA Polymerase {epsilon} Mutant That Specifically Causes +1 Frameshift Mutations Within Homonucleotide Runs in Yeast. Genetics
155: 1623-1632
[Abstract]
[Full Text]
-
Kruglyak, S., Durrett, R., Schug, M. D., Aquadro, C. F.
(2000). Distribution and Abundance of Microsatellites in the Yeast Genome Can Be Explained by a Balance Between Slippage Events and Point Mutations. Mol Biol Evol
17: 1210-1219
[Abstract]
[Full Text]
-
Vergnaud, G., Denoeud, F.
(2000). Minisatellites: Mutability and Genome Architecture. Genome Res
10: 899-907
[Abstract]
[Full Text]
-
Sokolsky, T., Alani, E.
(2000). EXO1 and MSH6 Are High-Copy Suppressors of Conditional Mutations in the MSH2 Mismatch Repair Gene of Saccharomyces cerevisiae. Genetics
155: 589-599
[Abstract]
[Full Text]
-
Jin, P., Warren, S. T.
(2000). Understanding the molecular basis of fragile X syndrome. Hum Mol Genet
9: 901-908
[Abstract]
[Full Text]
-
Iyer, R. R., Pluciennik, A., Rosche, W. A., Sinden, R. R., Wells, R. D.
(2000). DNA Polymerase III Proofreading Mutants Enhance the Expansion and Deletion of Triplet Repeat Sequences in Escherichia coli. J. Biol. Chem.
275: 2174-2184
[Abstract]
[Full Text]
-
Weisman-Shomer, P., Naot, Y., Fry, M.
(2000). Tetrahelical Forms of the Fragile X Syndrome Expanded Sequence d(CGG)n Are Destabilized by Two Heterogeneous Nuclear Ribonucleoprotein-related Telomeric DNA-binding Proteins. J. Biol. Chem.
275: 2231-2238
[Abstract]
[Full Text]
-
Chen, C., Merrill, B. J., Lau, P. J., Holm, C., Kolodner, R. D.
(1999). Saccharomyces cerevisiae pol30 (Proliferating Cell Nuclear Antigen) Mutations Impair Replication Fidelity and Mismatch Repair. Mol. Cell. Biol.
19: 7801-7815
[Abstract]
[Full Text]
-
Gary, R., Park, M. S., Nolan, J. P., Cornelius, H. L., Kozyreva, O. G., Tran, H. T., Lobachev, K. S., Resnick, M. A., Gordenin, D. A.
(1999). A Novel Role in DNA Metabolism for the Binding of Fen1/Rad27 to PCNA and Implications for Genetic Risk. Mol. Cell. Biol.
19: 5373-5382
[Abstract]
[Full Text]
-
White, P. J., Borts, R. H., Hirst, M. C.
(1999). Stability of the Human Fragile X (CGG)n Triplet Repeat Array in Saccharomyces cerevisiae Deficient in Aspects of DNA Metabolism. Mol. Cell. Biol.
19: 5675-5684
[Abstract]
[Full Text]
-
Schweitzer, J. K., Livingston, D. M.
(1999). The Effect of DNA Replication Mutations on CAG Tract Stability in Yeast. Genetics
152: 953-963
[Abstract]
[Full Text]
-
Parenteau, J., Wellinger, R. J.
(1999). Accumulation of Single-Stranded DNA and Destabilization of Telomeric Repeats in Yeast Mutant Strains Carrying a Deletion of RAD27. Mol. Cell. Biol.
19: 4143-4152
[Abstract]
[Full Text]
-
Paques, F., Haber, J. E.
(1999). Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev.
63: 349-404
[Abstract]
[Full Text]
-
Bebenek, A., Smith, L. A., Drake, J. W.
(1999). Bacteriophage T4 rnh (RNase H) Null Mutations: Effects on Spontaneous Mutation and Epistatic Interaction with rII Mutations. J. Bacteriol.
181: 3123-3128
[Abstract]
[Full Text]
-
Tran, H. T., Degtyareva, N. P., Gordenin, D. A., Resnick, M. A.
(1999). Genetic Factors Affecting the Impact of DNA Polymerase {delta} Proofreading Activity on Mutation Avoidance in Yeast. Genetics
152: 47-59
[Abstract]
[Full Text]
-
Tran, H. T., Gordenin, D. A., Resnick, M. A.
(1999). The 3'right-arrow5' Exonucleases of DNA Polymerases delta and varepsilon and the 5'right-arrow3' Exonuclease Exo1 Have Major Roles in Postreplication Mutation Avoidance in Saccharomyces cerevisiae. Mol. Cell. Biol.
19: 2000-2007
[Abstract]
[Full Text]
-
Moore, H., Greenwell, P. W., Liu, C.-P., Arnheim, N., Petes, T. D.
(1999). Triplet repeats form secondary structures that escape DNA repair in yeast. Proc. Natl. Acad. Sci. USA
96: 1504-1509
[Abstract]
[Full Text]
-
Liu, V. F., Bhaumik, D., Wang, T. S.-F.
(1999). Mutator Phenotype Induced by Aberrant Replication. Mol. Cell. Biol.
19: 1126-1135
[Abstract]
[Full Text]
-
Xie, Y., Counter, C., Alani, E.
(1999). Characterization of the Repeat-Tract Instability and Mutator Phenotypes Conferred by a Tn3 Insertion in RFC1, the Large Subunit of the Yeast Clamp Loader. Genetics
151: 499-509
[Abstract]
[Full Text]
-
Kokoska, R. J., Stefanovic, L., Buermeyer, A. B., Liskay, R. M., Petes, T. D.
(1999). A Mutation of the Yeast Gene Encoding PCNA Destabilizes Both Microsatellite and Minisatellite DNA Sequences. Genetics
151: 511-519
[Abstract]
[Full Text]
-
Miret, J. J., Pessoa-Brandao, L., Lahue, R. S.
(1998). Orientation-dependent and sequence-specific expansions of CTG/CAG trinucleotide repeats in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA
95: 12438-12443
[Abstract]
[Full Text]
-
da Silva, E. F., Reha-Krantz, L. J.
(2000). Dinucleotide Repeat Expansion Catalyzed by Bacteriophage T4 DNA Polymerase in Vitro. J. Biol. Chem.
275: 31528-31535
[Abstract]
[Full Text]
-
Jakupciak, J. P., Wells, R. D.
(2000). Gene Conversion (Recombination) Mediates Expansions of CTG{middle dot}CAG Repeats. J. Biol. Chem.
275: 40003-40013
[Abstract]
[Full Text]
-
Henricksen, L. A., Tom, S., Liu, Y., Bambara, R. A.
(2000). Inhibition of Flap Endonuclease 1 by Flap Secondary Structure and Relevance to Repeat Sequence Expansion. J. Biol. Chem.
275: 16420-16427
[Abstract]
[Full Text]
-
Jankowski, C., Nasar, F., Nag, D. K.
(2000). Meiotic instability of CAG repeat tracts occurs by double-strand break repair in yeast. Proc. Natl. Acad. Sci. USA
97: 2134-2139
[Abstract]
[Full Text]
-
Jin, Y. H., Obert, R., Burgers, P. M. J., Kunkel, T. A., Resnick, M. A., Gordenin, D. A.
(2001). The 3'right-arrow5' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability. Proc. Natl. Acad. Sci. USA
98: 5122-5127
[Abstract]
[Full Text]