Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 14 July 1995:
Vol. 269. no. 5221, pp. 238 - 240
DOI: 10.1126/science.7618086

Articles

Science, Vol 269, Issue 5221, 238-240
Copyright © 1995 by American Association for the Advancement of Science


articles

Requirement of the yeast RTH1 5' to 3' exonuclease for the stability of simple repetitive DNA

RE Johnson, GK Kovvali, L Prakash, and S Prakash

Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1061, USA.

Simple repetitive DNA sequences are unstable in human colorectal cancers and a variety of other cancers. Mutations in the DNA mismatch repair genes MSH2, MLH1, and PMS1 result in elevated rates of spontaneous mutation and cause a marked increase in the instability of simple repeats. Compared with the wild type, a null mutation in the yeast RTH1 gene, which encodes a 5' to 3' exonuclease, was shown to increase the rate of instability of simple repetitive DNA by as much as 280 times and to increase the spontaneous mutation rate by 30 times. Epistasis analyses were consistent with the hypothesis that this RTH1-encoded nuclease has a role in the MSH2-MLH-1-PMS1 mismatch repair pathway.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The MPH1 Gene of Saccharomyces cerevisiae Functions in Okazaki Fragment Processing.
Y.-H. Kang, M.-J. Kang, J.-H. Kim, C.-H. Lee, I.-t. Cho, J. Hurwitz, and Y.-S. Seo (2009)
J. Biol. Chem. 284, 10376-10386
   Abstract »    Full Text »    PDF »
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.
P. Singh, L. Zheng, V. Chavez, J. Qiu, and B. Shen (2007)
J. Biol. Chem. 282, 3465-3477
   Abstract »    Full Text »    PDF »
Interactions Among DNA Ligase I, the Flap Endonuclease and Proliferating Cell Nuclear Antigen in the Expansion and Contraction of CAG Repeat Tracts in Yeast.
E. W. Refsland and D. M. Livingston (2005)
Genetics 171, 923-934
   Abstract »    Full Text »    PDF »
Processing and Joining of DNA Ends Coordinated by Interactions among Dnl4/Lif1, Pol4, and FEN-1.
H.-M. Tseng and A. E. Tomkinson (2004)
J. Biol. Chem. 279, 47580-47588
   Abstract »    Full Text »    PDF »
Interaction Interface of Human Flap Endonuclease-1 with Its DNA Substrates.
J. Qiu, R. Liu, B. R. Chapados, M. Sherman, J. A. Tainer, and B. Shen (2004)
J. Biol. Chem. 279, 24394-24402
   Abstract »    Full Text »    PDF »
Triplet Repeat Expansion Generated by DNA Slippage Is Suppressed by Human Flap Endonuclease 1.
B. L. Ruggiero and M. D. Topal (2004)
J. Biol. Chem. 279, 23088-23097
   Abstract »    Full Text »    PDF »
Saccharomyces cerevisiae Flap Endonuclease 1 Uses Flap Equilibration To Maintain Triplet Repeat Stability.
Y. Liu, H. Zhang, J. Veeraraghavan, R. A. Bambara, and C. H. Freudenreich (2004)
Mol. Cell. Biol. 24, 4049-4064
   Abstract »    Full Text »    PDF »
WRN Helicase and FEN-1 Form a Complex upon Replication Arrest and Together Process Branchmigrating DNA Structures Associated with the Replication Fork.
S. Sharma, M. Otterlei, J. A. Sommers, H. C. Driscoll, G. L. Dianov, H.-I Kao, R. A. Bambara, and R. M. Brosh Jr. (2004)
Mol. Biol. Cell 15, 734-750
   Abstract »    Full Text »    PDF »
Effects of sequence on repeat expansion during DNA replication.
B. L. Heidenfelder and M. D. Topal (2003)
Nucleic Acids Res. 31, 7159-7164
   Abstract »    Full Text »    PDF »
Mutations in Yeast Replication Proteins That Increase CAG/CTG Expansions Also Increase Repeat Fragility.
J. L. Callahan, K. J. Andrews, V. A. Zakian, and C. H. Freudenreich (2003)
Mol. Cell. Biol. 23, 7849-7860
   Abstract »    Full Text »    PDF »
Nuclease-Deficient FEN-1 Blocks Rad51/BRCA1-Mediated Repair and Causes Trinucleotide Repeat Instability.
C. Spiro and C. T. McMurray (2003)
Mol. Cell. Biol. 23, 6063-6074
   Abstract »    Full Text »    PDF »
Analysis of Human Flap Endonuclease 1 Mutants Reveals a Mechanism to Prevent Triplet Repeat Expansion.
Y. Liu and R. A. Bambara (2003)
J. Biol. Chem. 278, 13728-13739
   Abstract »    Full Text »    PDF »
Okazaki Fragment Maturation in Yeast. I. DISTRIBUTION OF FUNCTIONS BETWEEN FEN1 AND DNA2.
R. Ayyagari, X. V. Gomes, D. A. Gordenin, and P. M. J. Burgers (2003)
J. Biol. Chem. 278, 1618-1625
   Abstract »    Full Text »    PDF »
Differential Processing of Leading- and Lagging-Strand Ends at Saccharomyces cerevisiae Telomeres Revealed by the Absence of Rad27p Nuclease.
J. Parenteau and R. J. Wellinger (2002)
Genetics 162, 1583-1594
   Abstract »    Full Text »    PDF »
Identification of RTG2 as a Modifier Gene for CTG{middle dot}CAG Repeat Instability in Saccharomyces cerevisiae.
S. Bhattacharyya, M. L. Rolfsmeier, M. J. Dixon, K. Wagoner, and R. S. Lahue (2002)
Genetics 162, 579-589
   Abstract »    Full Text »    PDF »
Vertebrate cells lacking FEN-1 endonuclease are viable but hypersensitive to methylating agents and H2O2.
Y. Matsuzaki, N. Adachi, and H. Koyama (2002)
Nucleic Acids Res. 30, 3273-3277
   Abstract »    Full Text »    PDF »
Arginine Residues 47 and 70 of Human Flap Endonuclease-1 Are Involved in DNA Substrate Interactions and Cleavage Site Determination.
J. Qiu, D. N. Bimston, A. Partikian, and B. Shen (2002)
J. Biol. Chem. 277, 24659-24666
   Abstract »    Full Text »    PDF »
Human Exonuclease I Is Required for 5' and 3' Mismatch Repair.
J. Genschel, L. R. Bazemore, and P. Modrich (2002)
J. Biol. Chem. 277, 13302-13311
   Abstract »    Full Text »    PDF »
The Roles of Klenow Processing and Flap Processing Activities of DNA Polymerase I in Chromosome Instability in Escherichia coli K12 Strains.
Y. Nagata, K. Mashimo, M. Kawata, and K. Yamamoto (2002)
Genetics 160, 13-23
   Abstract »    Full Text »    PDF »
Isolation and Characterization of Point Mutations in Mismatch Repair Genes That Destabilize Microsatellites in Yeast.
E. A. Sia, M. Dominska, L. Stefanovic, and T. D. Petes (2001)
Mol. Cell. Biol. 21, 8157-8167
   Abstract »    Full Text »    PDF »
Identification of rad27 Mutations That Confer Differential Defects in Mutation Avoidance, Repeat Tract Instability, and Flap Cleavage.
Y. Xie, Y. Liu, J. L. Argueso, L. A. Henricksen, H.-I Kao, R. A. Bambara, and E. Alani (2001)
Mol. Cell. Biol. 21, 4889-4899
   Abstract »    Full Text »    PDF »
Meiotic Recombination Involving Heterozygous Large Insertions in Saccharomyces cerevisiae: Formation and Repair of Large, Unpaired DNA Loops.
H. M. Kearney, D. T. Kirkpatrick, J. L. Gerton, and T. D. Petes (2001)
Genetics 158, 1457-1476
   Abstract »    Full Text »    PDF »
Links between replication and recombination in Saccharomyces cerevisiae: A hypersensitive requirement for homologous recombination in the absence of Rad27 activity.
H. Debrauwere, S. Loeillet, W. Lin, J. Lopes, and A. Nicolas (2001)
PNAS 98, 8263-8269
   Abstract »    Full Text »    PDF »
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.
R. J. Kokoska, L. Stefanovic, J. DeMai, and T. D. Petes (2000)
Mol. Cell. Biol. 20, 7490-7504
   Abstract »    Full Text »
Mutational spectrum analysis of RNase H(35) deficient Saccharomyces cerevisiae using fluorescence-based directed termination PCR.
J. Z. Chen, J. Qiu, B. Shen, and G. P. Holmquist (2000)
Nucleic Acids Res. 28, 3649-3656
   Abstract »    Full Text »    PDF »
The nature of the 5'-terminus is a major determinant for DNA processing by Schizosaccharomyces pombe Rad2p, a FEN-1 family nuclease.
J. L. Alleva and P. W. Doetsch (2000)
Nucleic Acids Res. 28, 2893-2901
   Abstract »    Full Text »    PDF »
A DNA Polymerase {epsilon} Mutant That Specifically Causes +1 Frameshift Mutations Within Homonucleotide Runs in Yeast.
J. M. Kirchner, H. Tran, and M. A. Resnick (2000)
Genetics 155, 1623-1632
   Abstract »    Full Text »
Genetic Analyses of Schizosaccharomyces pombe dna2+ Reveal That Dna2 Plays an Essential Role in Okazaki Fragment Metabolism.
H.-Y. Kang, E. Choi, S.-H. Bae, K.-H. Lee, B.-S. Gim, H.-D. Kim, C. Park, S. A. MacNeill, and Y.-S. Seo (2000)
Genetics 155, 1055-1067
   Abstract »    Full Text »
Understanding the molecular basis of fragile X syndrome.
P. Jin and S. T. Warren (2000)
Hum. Mol. Genet. 9, 901-908
   Abstract »    Full Text »    PDF »
Identification of the Xenopus laevis Homolog of Saccharomyces cerevisiae DNA2 and Its Role in DNA Replication.
Q. Liu, W.-c. Choe, and J. L. Campbell (2000)
J. Biol. Chem. 275, 1615-1624
   Abstract »    Full Text »    PDF »
The RAD2 Domain of Human Exonuclease 1 Exhibits 5' to 3' Exonuclease and Flap Structure-specific Endonuclease Activities.
B.-I. Lee and D. M. Wilson III (1999)
J. Biol. Chem. 274, 37763-37769
   Abstract »    Full Text »    PDF »
A Novel Role in DNA Metabolism for the Binding of Fen1/Rad27 to PCNA and Implications for Genetic Risk.
R. Gary, M. S. Park, J. P. Nolan, H. L. Cornelius, O. G. Kozyreva, H. T. Tran, K. S. Lobachev, M. A. Resnick, and D. A. Gordenin (1999)
Mol. Cell. Biol. 19, 5373-5382
   Abstract »    Full Text »    PDF »
Stability of the Human Fragile X (CGG)n Triplet Repeat Array in Saccharomyces cerevisiae Deficient in Aspects of DNA Metabolism.
P. J. White, R. H. Borts, and M. C. Hirst (1999)
Mol. Cell. Biol. 19, 5675-5684
   Abstract »    Full Text »    PDF »
Human Exonuclease 1 Functionally Complements Its Yeast Homologues in DNA Recombination, RNA Primer Removal, and Mutation Avoidance.
J. Qiu, Y. Qian, V. Chen, M.-X. Guan, and B. Shen (1999)
J. Biol. Chem. 274, 17893-17900
   Abstract »    Full Text »    PDF »
Accumulation of Single-Stranded DNA and Destabilization of Telomeric Repeats in Yeast Mutant Strains Carrying a Deletion of RAD27.
J. Parenteau and R. J. Wellinger (1999)
Mol. Cell. Biol. 19, 4143-4152
   Abstract »    Full Text »    PDF »
Cleavage of Substrates with Mismatched Nucleotides by Flap Endonuclease-1. IMPLICATIONS FOR MAMMALIAN OKAZAKI FRAGMENT PROCESSING.
J. A. Rumbaugh, L. A. Henricksen, M. S. DeMott, and R. A. Bambara (1999)
J. Biol. Chem. 274, 14602-14608
   Abstract »    Full Text »    PDF »
Bacteriophage T4 rnh (RNase H) Null Mutations: Effects on Spontaneous Mutation and Epistatic Interaction with rII Mutations.
A. Bebenek, L. A. Smith, and J. W. Drake (1999)
J. Bacteriol. 181, 3123-3128
   Abstract »    Full Text »
Genetic Factors Affecting the Impact of DNA Polymerase {delta} Proofreading Activity on Mutation Avoidance in Yeast.
H. T. Tran, N. P. Degtyareva, D. A. Gordenin, and M. A. Resnick (1999)
Genetics 152, 47-59
   Abstract »    Full Text »
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.
H. T. Tran, D. A. Gordenin, and M. A. Resnick (1999)
Mol. Cell. Biol. 19, 2000-2007
   Abstract »    Full Text »    PDF »
A role for FEN-1 in nonhomologous DNA end joining: The order of strand annealing and nucleolytic processing events.
X. Wu, T. E. Wilson, and M. R. Lieber (1999)
PNAS 96, 1303-1308
   Abstract »    Full Text »    PDF »
Characterization of the Repeat-Tract Instability and Mutator Phenotypes Conferred by a Tn3 Insertion in RFC1, the Large Subunit of the Yeast Clamp Loader.
Y. Xie, C. Counter, and E. Alani (1999)
Genetics 151, 499-509
   Abstract »    Full Text »
A Mutation of the Yeast Gene Encoding PCNA Destabilizes Both Microsatellite and Minisatellite DNA Sequences.
R. J. Kokoska, L. Stefanovic, A. B. Buermeyer, R. M. Liskay, and T. D. Petes (1999)
Genetics 151, 511-519
   Abstract »    Full Text »
Structural Changes Measured by X-ray Scattering from Human Flap Endonuclease-1 Complexed with Mg2+ and Flap DNA Substrate.
C.-Y. Kim, B. Shen, M. S. Park, and G. A. Olah (1999)
J. Biol. Chem. 274, 1233-1239
   Abstract »    Full Text »    PDF »
Partial Functional Deficiency of E160D Flap Endonuclease-1 Mutant in Vitro and in Vivo Is Due to Defective Cleavage of DNA Substrates.
G. Frank, J. Qiu, M. Somsouk, Y. Weng, L. Somsouk, J. P. Nolan, and B. Shen (1998)
J. Biol. Chem. 273, 33064-33072
   Abstract »    Full Text »    PDF »
Processing of an HIV Replication Intermediate by the Human DNA Replication Enzyme FEN1.
J. A. Rumbaugh, G. M. Fuentes, and R. A. Bambara (1998)
J. Biol. Chem. 273, 28740-28745
   Abstract »    Full Text »    PDF »
Newly Discovered Archaebacterial Flap Endonucleases Show a Structure-Specific Mechanism for DNA Substrate Binding and Catalysis Resembling Human Flap Endonuclease-1.
D. J. Hosfield, G. Frank, Y. Weng, J. A. Tainer, and B. Shen (1998)
J. Biol. Chem. 273, 27154-27161
   Abstract »    Full Text »    PDF »
The role of SOS and flap processing in microsatellite instability in Escherichia coli.
P. Morel, C. Reverdy, B. M. S. D. Ehrlich, E. Cassuto, and E. Cassuto (1998)
PNAS 95, 10003-10008
   Abstract »    Full Text »    PDF »
Mapping the Polarity of Changes That Occur in Interrupted CAG Repeat Tracts in Yeast.
D. J. Maurer, B. L. O'Callaghan, and D. M. Livingston (1998)
Mol. Cell. Biol. 18, 4597-4604
   Abstract »    Full Text »
Destabilization of Yeast Micro- and Minisatellite DNA Sequences by Mutations Affecting a Nuclease Involved in Okazaki Fragment Processing (rad27) and DNA Polymerase delta  (pol3-t).
R. J. Kokoska, L. Stefanovic, H. T. Tran, M. A. Resnick, D. A. Gordenin, and T. D. Petes (1998)
Mol. Cell. Biol. 18, 2779-2788
   Abstract »    Full Text »
Junction ribonuclease: An activity in Okazaki fragment processing.
R. S. Murante, L. A. Henricksen, and R. A. Bambara (1998)
PNAS 95, 2244-2249
   Abstract »    Full Text »    PDF »
Expansion and Length-Dependent Fragility of CTG Repeats in Yeast.
C. H. Freudenreich, S. M. Kantrow, and V. A. Zakian (1998)
Science 279, 853-856
   Abstract »    Full Text »
The RAD52 Recombinational Repair Pathway is Essential in pol30 (PCNA) Mutants That Accumulate Small Single-Stranded DNA Fragments During DNA Synthesis.
B. J. Merrill and C. Holm (1998)
Genetics 148, 611-624
   Abstract »    Full Text »    PDF »
The 5'-Exonuclease Activity of Bacteriophage T4 RNase H Is Stimulated by the T4 Gene 32 Single-stranded DNA-binding Protein, but Its Flap Endonuclease Is Inhibited.
M. Bhagwat, L. J. Hobbs, and N. G. Nossal (1997)
J. Biol. Chem. 272, 28523-28530
   Abstract »    Full Text »    PDF »
Strand-specific Mismatch Repair in Mammalian Cells.
P. Modrich (1997)
J. Biol. Chem. 272, 24727-24730
   Full Text »    PDF »
Molecular Mechanism of Base Excision Repair of Uracil-containing DNA in Yeast Cell-free Extracts.
Z. Wang, X. Wu, and E. C. Friedberg (1997)
J. Biol. Chem. 272, 24064-24071
   Abstract »    Full Text »    PDF »
Identification and characterization of Saccharomyces cerevisiae EXO1, a gene encoding an exonuclease that interacts with MSH2.
D. X. Tishkoff, A. L. Boerger, P. Bertrand, N. Filosi, G. M. Gaida, M. F. Kane, and R. D. Kolodner (1997)
PNAS 94, 7487-7492
   Abstract »    Full Text »    PDF »
Cleavage of Insertion/Deletion Mismatches, Flap and Pseudo-Y DNA Structures by Deoxyinosine 3'-Endonuclease from Escherichia coli.
M. Yao and Y. W. Kow (1996)
J. Biol. Chem. 271, 30672-30676
   Abstract »    Full Text »    PDF »
Mechanism of Tracking and Cleavage of Adduct-damaged DNA Substrates by the Mammalian 5'- to 3'-Exonuclease/Endonuclease RAD2 Homologue 1or Flap Endonuclease 1.
C. J. Barnes, A. F. Wahl, B. Shen, M. S. Park, and R. A. Bambara (1996)
J. Biol. Chem. 271, 29624-29631
   Abstract »    Full Text »    PDF »
Calf RTH-1 Nuclease Can Remove the Initiator RNAs of Okazaki Fragments by Endonuclease Activity.
R. S. Murante, J. A. Rumbaugh, C. J. Barnes, J. R. Norton, and R. A. Bambara (1996)
J. Biol. Chem. 271, 25888-25897
   Abstract »    Full Text »    PDF »
Biochemistry and genetics of eukaryotic mismatch repair..
R Kolodner (1996)
Genes & Dev. 10, 1433-1442
   PDF »
A novel mechanism for telomere size control in Saccharomyces cerevisiae..
B Li and A J Lustig (1996)
Genes & Dev. 10, 1310-1326
   Abstract »    PDF »
Replication Protein A Confers Structure-specific Endonuclease Activities to the XPF-ERCC1 and XPG Subunits of Human DNA Repair Excision Nuclease.
T. Matsunaga, C.-H. Park, T. Bessho, D. Mu, and A. Sancar (1996)
J. Biol. Chem. 271, 11047-11050
   Abstract »    Full Text »    PDF »
Essential Amino Acids for Substrate Binding and Catalysis of Human Flap Endonuclease 1.
B. Shen, J. P. Nolan, L. A. Sklar, and M. S. Park (1996)
J. Biol. Chem. 271, 9173-9176
   Abstract »    Full Text »    PDF »
Requirement of the Yeast MSH3 and MSH6 Genes for MSH2-dependent Genomic Stability.
R. E. Johnson, G. K. Kovvali, L. Prakash, and S. Prakash (1996)
J. Biol. Chem. 271, 7285-7288
   Abstract »    Full Text »    PDF »
Structure-specific Nuclease Activity in Yeast Nucleotide Excision Repair Protein Rad2.
Y. Habraken, P. Sung, L. Prakash, and S. Prakash (1995)
J. Biol. Chem. 270, 30194-30198
   Abstract »    Full Text »    PDF »
RNA Template-dependent 5' Nuclease Activity of Thermus aquaticus and Thermus thermophilus DNA Polymerases.
W.-P. Ma, M. W. Kaiser, N. Lyamicheva, J. J. Schaefer, H. T. Allawi, T. Takova, B. P. Neri, and V. I. Lyamichev (2000)
J. Biol. Chem. 275, 24693-24700
   Abstract »    Full Text »    PDF »
Dinucleotide Repeat Expansion Catalyzed by Bacteriophage T4 DNA Polymerase in Vitro.
E. F. da Silva and L. J. Reha-Krantz (2000)
J. Biol. Chem. 275, 31528-31535
   Abstract »    Full Text »    PDF »
Characterization of the Enzymatic Properties of the Yeast Dna2 Helicase/Endonuclease Suggests a New Model for Okazaki Fragment Processing.
S.-H. Bae and Y.-S. Seo (2000)
J. Biol. Chem. 275, 38022-38031
   Abstract »    Full Text »    PDF »
Modeling the Late Steps in HIV-1 Retroviral Integrase-catalyzed DNA Integration.
E. Brin, J. Yi, A. M. Skalka, and J. Leis (2000)
J. Biol. Chem. 275, 39287-39295
   Abstract »    Full Text »    PDF »
Cell Cycle-dependent and DNA Damage-inducible Nuclear Localization of FEN-1 Nuclease Is Consistent with Its Dual Functions in DNA Replication and Repair.
J. Qiu, X. Li, G. Frank, and B. Shen (2001)
J. Biol. Chem. 276, 4901-4908
   Abstract »    Full Text »    PDF »
The Interaction of DNA Mismatch Repair Proteins with Human Exonuclease I.
C. Schmutte, M. M. Sadoff, K.-S. Shim, S. Acharya, and R. Fishel (2001)
J. Biol. Chem. 276, 33011-33018
   Abstract »    Full Text »    PDF »
Stimulation of Eukaryotic Flap Endonuclease-1 Activities by Proliferating Cell Nuclear Antigen (PCNA) Is Independent of Its in Vitro Interaction via a Consensus PCNA Binding Region.
G. Frank, J. Qiu, L. Zheng, and B. Shen (2001)
J. Biol. Chem. 276, 36295-36302
   Abstract »    Full Text »    PDF »
The Nuclease Activity of the Yeast Dna2 Protein, Which Is Related to the RecB-like Nucleases, Is Essential in Vivo.
M. E. Budd, W.-c. Choe, and J. L. Campbell (2000)
J. Biol. Chem. 275, 16518-16529
   Abstract »    Full Text »    PDF »
Inhibition of Flap Endonuclease 1 by Flap Secondary Structure and Relevance to Repeat Sequence Expansion.
L. A. Henricksen, S. Tom, Y. Liu, and R. A. Bambara (2000)
J. Biol. Chem. 275, 16420-16427
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)