Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 Oct;9(10):4432–4440. doi: 10.1128/mcb.9.10.4432

Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.

B Kramer 1, W Kramer 1, M S Williamson 1, S Fogel 1
PMCID: PMC362526  PMID: 2685551

Abstract

In vitro-constructed heteroduplex DNAs with defined mismatches were corrected in Saccharomyces cerevisiae cells with efficiencies that were dependent on the mismatch. Single-nucleotide loops were repaired very efficiently; the base/base mismatches G/T, A/C, G/G, A/G, G/A, A/A, T/T, T/C, and C/T were repaired with a high to intermediate efficiency. The mismatch C/C and a 38-nucleotide loop were corrected with low efficiency. This substrate specificity pattern resembles that found in Escherichia coli and Streptococcus pneumoniae, suggesting an evolutionary relationship of DNA mismatch repair in pro- and eucaryotes. Repair of the listed mismatches was severely impaired in the putative S. cerevisiae DNA mismatch repair mutants pms1 and pms2. Low-efficiency repair also characterized pms3 strains, except that correction of single-nucleotide loops occurred with an efficiency close to that of PMS wild-type strains. A close correlation was found between the repair efficiencies determined in this study and the observed postmeiotic segregation frequencies of alleles with known DNA sequence. This suggests an involvement of DNA mismatch repair in recombination and gene conversion in S. cerevisiae.

Full text

PDF
4432

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balganesh T. S., Lacks S. A. Heteroduplex DNA mismatch repair system of Streptococcus pneumoniae: cloning and expression of the hexA gene. J Bacteriol. 1985 Jun;162(3):979–984. doi: 10.1128/jb.162.3.979-984.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bankier A. T., Weston K. M., Barrell B. G. Random cloning and sequencing by the M13/dideoxynucleotide chain termination method. Methods Enzymol. 1987;155:51–93. doi: 10.1016/0076-6879(87)55009-1. [DOI] [PubMed] [Google Scholar]
  3. Beacham I. R., Schweitzer B. W., Warrick H. M., Carbon J. The nucleotide sequence of the yeast ARG4 gene. Gene. 1984 Sep;29(3):271–279. doi: 10.1016/0378-1119(84)90056-8. [DOI] [PubMed] [Google Scholar]
  4. Bishop D. K., Kolodner R. D. Repair of heteroduplex plasmid DNA after transformation into Saccharomyces cerevisiae. Mol Cell Biol. 1986 Oct;6(10):3401–3409. doi: 10.1128/mcb.6.10.3401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bishop D. K., Williamson M. S., Fogel S., Kolodner R. D. The role of heteroduplex correction in gene conversion in Saccharomyces cerevisiae. Nature. 1987 Jul 23;328(6128):362–364. doi: 10.1038/328362a0. [DOI] [PubMed] [Google Scholar]
  6. Boeke J. D., Trueheart J., Natsoulis G., Fink G. R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. doi: 10.1016/0076-6879(87)54076-9. [DOI] [PubMed] [Google Scholar]
  7. Borts R. H., Haber J. E. Meiotic recombination in yeast: alteration by multiple heterozygosities. Science. 1987 Sep 18;237(4821):1459–1465. doi: 10.1126/science.2820060. [DOI] [PubMed] [Google Scholar]
  8. Brown T. C., Jiricny J. Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell. 1988 Aug 26;54(5):705–711. doi: 10.1016/s0092-8674(88)80015-1. [DOI] [PubMed] [Google Scholar]
  9. Bruni R., Martin D., Jiricny J. d(GATC) sequences influence Escherichia coli mismatch repair in a distance-dependent manner from positions both upstream and downstream of the mismatch. Nucleic Acids Res. 1988 Jun 10;16(11):4875–4890. doi: 10.1093/nar/16.11.4875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Campbell D. A., Fogel S., Lusnak K. Mitotic chromosome loss in a disomic haploid of Saccharomyces cerevisiae. Genetics. 1975 Mar;79(3):383–396. doi: 10.1093/genetics/79.3.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  12. Claverys J. P., Lacks S. A. Heteroduplex deoxyribonucleic acid base mismatch repair in bacteria. Microbiol Rev. 1986 Jun;50(2):133–165. doi: 10.1128/mr.50.2.133-165.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Claverys J. P., Méjean V., Gasc A. M., Sicard A. M. Mismatch repair in Streptococcus pneumoniae: relationship between base mismatches and transformation efficiencies. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5956–5960. doi: 10.1073/pnas.80.19.5956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Culbertson M. R., Charnas L., Johnson M. T., Fink G. R. Frameshifts and frameshift suppressors in Saccharomyces cerevisiae. Genetics. 1977 Aug;86(4):745–764. doi: 10.1093/genetics/86.4.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dente L., Cesareni G., Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. doi: 10.1093/nar/11.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dohet C., Dzidić S., Wagner R., Radman M. Large non-homology in heteroduplex DNA is processed differently than single base pair mismatches. Mol Gen Genet. 1987 Jan;206(1):181–184. doi: 10.1007/BF00326556. [DOI] [PubMed] [Google Scholar]
  17. Dohet C., Wagner R., Radman M. Repair of defined single base-pair mismatches in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Jan;82(2):503–505. doi: 10.1073/pnas.82.2.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Doutriaux M. P., Wagner R., Radman M. Mismatch-stimulated killing. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2576–2578. doi: 10.1073/pnas.83.8.2576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Esposito M. S. X-ray and meiotic fine structure mapping of the adenine-8 locus in Saccharomyces cerevisiae. Genetics. 1968 Apr;58(4):507–527. doi: 10.1093/genetics/58.4.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fogel S., Mortimer R., Lusnak K., Tavares F. Meiotic gene conversion: a signal of the basic recombination event in yeast. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):1325–1341. doi: 10.1101/sqb.1979.043.01.152. [DOI] [PubMed] [Google Scholar]
  21. Geier G. E., Modrich P. Recognition sequence of the dam methylase of Escherichia coli K12 and mode of cleavage of Dpn I endonuclease. J Biol Chem. 1979 Feb 25;254(4):1408–1413. [PubMed] [Google Scholar]
  22. Haber L. T., Pang P. P., Sobell D. I., Mankovich J. A., Walker G. C. Nucleotide sequence of the Salmonella typhimurium mutS gene required for mismatch repair: homology of MutS and HexA of Streptococcus pneumoniae. J Bacteriol. 1988 Jan;170(1):197–202. doi: 10.1128/jb.170.1.197-202.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hastings P. J. Measurement of restoration and conversion: its meaning for the mismatch repair hypothesis of conversion. Cold Spring Harb Symp Quant Biol. 1984;49:49–53. doi: 10.1101/sqb.1984.049.01.008. [DOI] [PubMed] [Google Scholar]
  24. Hoekstra M. F., Malone R. E. Excision repair functions in Saccharomyces cerevisiae recognize and repair methylation of adenine by the Escherichia coli dam gene. Mol Cell Biol. 1986 Oct;6(10):3555–3558. doi: 10.1128/mcb.6.10.3555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Johnston L. H., Nasmyth K. A. Saccharomyces cerevisiae cell cycle mutant cdc9 is defective in DNA ligase. Nature. 1978 Aug 31;274(5674):891–893. doi: 10.1038/274891a0. [DOI] [PubMed] [Google Scholar]
  27. Jones M., Wagner R., Radman M. Repair of a mismatch is influenced by the base composition of the surrounding nucleotide sequence. Genetics. 1987 Apr;115(4):605–610. doi: 10.1093/genetics/115.4.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Judd S. R., Petes T. D. Physical lengths of meiotic and mitotic gene conversion tracts in Saccharomyces cerevisiae. Genetics. 1988 Mar;118(3):401–410. doi: 10.1093/genetics/118.3.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kan L. S., Chandrasegaran S., Pulford S. M., Miller P. S. Detection of a guanine X adenine base pair in a decadeoxyribonucleotide by proton magnetic resonance spectroscopy. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4263–4265. doi: 10.1073/pnas.80.14.4263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kennard O. Structural studies of DNA fragments: the G.T wobble base pair in A, B and Z DNA; the G.A base pair in B-DNA. J Biomol Struct Dyn. 1985 Oct;3(2):205–226. doi: 10.1080/07391102.1985.10508412. [DOI] [PubMed] [Google Scholar]
  31. Kramer B., Kramer W., Fritz H. J. Different base/base mismatches are corrected with different efficiencies by the methyl-directed DNA mismatch-repair system of E. coli. Cell. 1984 Oct;38(3):879–887. doi: 10.1016/0092-8674(84)90283-6. [DOI] [PubMed] [Google Scholar]
  32. Kramer W., Fritz H. J. Oligonucleotide-directed construction of mutations via gapped duplex DNA. Methods Enzymol. 1987;154:350–367. doi: 10.1016/0076-6879(87)54084-8. [DOI] [PubMed] [Google Scholar]
  33. Lacks S. A., Dunn J. J., Greenberg B. Identification of base mismatches recognized by the heteroduplex-DNA-repair system of Streptococcus pneumoniae. Cell. 1982 Dec;31(2 Pt 1):327–336. doi: 10.1016/0092-8674(82)90126-x. [DOI] [PubMed] [Google Scholar]
  34. Lu A. L., Chang D. Y. A novel nucleotide excision repair for the conversion of an A/G mismatch to C/G base pair in E. coli. Cell. 1988 Sep 9;54(6):805–812. doi: 10.1016/s0092-8674(88)91109-9. [DOI] [PubMed] [Google Scholar]
  35. Lu A. L., Chang D. Y. Repair of single base-pair transversion mismatches of Escherichia coli in vitro: correction of certain A/G mismatches is independent of dam methylation and host mutHLS gene functions. Genetics. 1988 Apr;118(4):593–600. doi: 10.1093/genetics/118.4.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lu A. L., Clark S., Modrich P. Methyl-directed repair of DNA base-pair mismatches in vitro. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4639–4643. doi: 10.1073/pnas.80.15.4639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lu A. L., Welsh K., Clark S., Su S. S., Modrich P. Repair of DNA base-pair mismatches in extracts of Escherichia coli. Cold Spring Harb Symp Quant Biol. 1984;49:589–596. doi: 10.1101/sqb.1984.049.01.066. [DOI] [PubMed] [Google Scholar]
  38. Längle-Rouault F., Maenhaut-Michel G., Radman M. GATC sequences, DNA nicks and the MutH function in Escherichia coli mismatch repair. EMBO J. 1987 Apr;6(4):1121–1127. doi: 10.1002/j.1460-2075.1987.tb04867.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Maloney D. H., Fogel S. Gene conversion, unequal crossing-over and mispairing at a non-tandem duplication during meiosis of Saccharomyces cerevisiae. Curr Genet. 1987;12(1):1–7. doi: 10.1007/BF00420720. [DOI] [PubMed] [Google Scholar]
  40. Marinus M. G., Morris N. R. Isolation of deoxyribonucleic acid methylase mutants of Escherichia coli K-12. J Bacteriol. 1973 Jun;114(3):1143–1150. doi: 10.1128/jb.114.3.1143-1150.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Meselson M. S., Radding C. M. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. doi: 10.1073/pnas.72.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Modrich P. DNA mismatch correction. Annu Rev Biochem. 1987;56:435–466. doi: 10.1146/annurev.bi.56.070187.002251. [DOI] [PubMed] [Google Scholar]
  43. Moore C. W., Hampsey D. M., Ernst J. F., Sherman F. Differential mismatch repair can explain the disproportionalities between physical distances and recombination frequencies of cyc1 mutations in yeast. Genetics. 1988 May;119(1):21–34. doi: 10.1093/genetics/119.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Mostachfi P., Sicard A. M. Polarity of localised conversion in Streptococcus pneumoniae transformation. Mol Gen Genet. 1987 Jun;208(1-2):361–363. doi: 10.1007/BF00330467. [DOI] [PubMed] [Google Scholar]
  45. Muster-Nassal C., Kolodner R. Mismatch correction catalyzed by cell-free extracts of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7618–7622. doi: 10.1073/pnas.83.20.7618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Patel D. J., Kozlowski S. A., Ikuta S., Itakura K. Deoxyguanosine-deoxyadenosine pairing in the d(C-G-A-G-A-A-T-T-C-G-C-G) duplex: conformation and dynamics at and adjacent to the dG X dA mismatch site. Biochemistry. 1984 Jul 3;23(14):3207–3217. doi: 10.1021/bi00309a015. [DOI] [PubMed] [Google Scholar]
  47. Priebe S. D., Hadi S. M., Greenberg B., Lacks S. A. Nucleotide sequence of the hexA gene for DNA mismatch repair in Streptococcus pneumoniae and homology of hexA to mutS of Escherichia coli and Salmonella typhimurium. J Bacteriol. 1988 Jan;170(1):190–196. doi: 10.1128/jb.170.1.190-196.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Proffitt J. H., Davie J. R., Swinton D., Hattman S. 5-Methylcytosine is not detectable in Saccharomyces cerevisiae DNA. Mol Cell Biol. 1984 May;4(5):985–988. doi: 10.1128/mcb.4.5.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Radman M., Wagner R. Mismatch repair in Escherichia coli. Annu Rev Genet. 1986;20:523–538. doi: 10.1146/annurev.ge.20.120186.002515. [DOI] [PubMed] [Google Scholar]
  50. Rose M. D., Novick P., Thomas J. H., Botstein D., Fink G. R. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. doi: 10.1016/0378-1119(87)90232-0. [DOI] [PubMed] [Google Scholar]
  51. Stanssens P., Opsomer C., McKeown Y. M., Kramer W., Zabeau M., Fritz H. J. Efficient oligonucleotide-directed construction of mutations in expression vectors by the gapped duplex DNA method using alternating selectable markers. Nucleic Acids Res. 1989 Jun 26;17(12):4441–4454. doi: 10.1093/nar/17.12.4441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Su S. S., Lahue R. S., Au K. G., Modrich P. Mispair specificity of methyl-directed DNA mismatch correction in vitro. J Biol Chem. 1988 May 15;263(14):6829–6835. [PubMed] [Google Scholar]
  53. Su S. S., Modrich P. Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5057–5061. doi: 10.1073/pnas.83.14.5057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Szostak J. W., Orr-Weaver T. L., Rothstein R. J., Stahl F. W. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. doi: 10.1016/0092-8674(83)90331-8. [DOI] [PubMed] [Google Scholar]
  55. Vieira J., Messing J. Production of single-stranded plasmid DNA. Methods Enzymol. 1987;153:3–11. doi: 10.1016/0076-6879(87)53044-0. [DOI] [PubMed] [Google Scholar]
  56. Wagner R., Dohet C., Jones M., Doutriaux M. P., Hutchinson F., Radman M. Involvement of Escherichia coli mismatch repair in DNA replication and recombination. Cold Spring Harb Symp Quant Biol. 1984;49:611–615. doi: 10.1101/sqb.1984.049.01.069. [DOI] [PubMed] [Google Scholar]
  57. Welsh K. M., Lu A. L., Clark S., Modrich P. Isolation and characterization of the Escherichia coli mutH gene product. J Biol Chem. 1987 Nov 15;262(32):15624–15629. [PubMed] [Google Scholar]
  58. White J. H., DiMartino J. F., Anderson R. W., Lusnak K., Hilbert D., Fogel S. A DNA sequence conferring high postmeiotic segregation frequency to heterozygous deletions in Saccharomyces cerevisiae is related to sequences associated with eucaryotic recombination hotspots. Mol Cell Biol. 1988 Mar;8(3):1253–1258. doi: 10.1128/mcb.8.3.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. White J. H., Lusnak K., Fogel S. Mismatch-specific post-meiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate. Nature. 1985 May 23;315(6017):350–352. doi: 10.1038/315350a0. [DOI] [PubMed] [Google Scholar]
  60. Williamson M. S., Game J. C., Fogel S. Meiotic gene conversion mutants in Saccharomyces cerevisiae. I. Isolation and characterization of pms1-1 and pms1-2. Genetics. 1985 Aug;110(4):609–646. doi: 10.1093/genetics/110.4.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES