Systematic mutagenesis of the Saccharomyces cerevisiae MLH1 gene reveals distinct roles for Mlh1p in meiotic crossing over and in vegetative and meiotic mismatch repair

Molecular and Cellular Biology

Volumn 23, Issue 3, 2003, Pages 873-886

  Argueso, Juan Lucas ^a   Kijas, Amanda Wraith ^a   Sarin, Sumeet ^a,b   Heck, Julie ^a   Waase, Marc ^a,c   Alani, Eric ^a  

^a Cornell University ^*  (United States)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; PROTEIN; PROTEIN MLH1; PROTEIN MLH1P; PROTEIN MUTL; PROTEIN MUTS; PROTEIN PMS1P; UNCLASSIFIED DRUG;

ALLELE; ARTICLE; CHROMOSOME SEGREGATION; CROSSING OVER; ENZYME ACTIVITY; EUKARYOTIC CELL; FUNGUS SPORE; GENE MUTATION; GENE SEGREGATION; GENETIC POLYMORPHISM; GENETIC RECOMBINATION; HOLLIDAY JUNCTION; MEIOSIS; MISMATCH REPAIR; MUTAGENESIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN MOTIF; PROTEIN PROCESSING; PROTEIN STRUCTURE; SACCHAROMYCES CEREVISIAE; STRUCTURE ACTIVITY RELATION; VEGETATIVE GROWTH;

ADENOSINE TRIPHOSPHATASES; ADENOSINE TRIPHOSPHATE; ALLELES; BASE PAIR MISMATCH; CARRIER PROTEINS; CROSSING OVER, GENETIC; DNA REPAIR; FUNGAL PROTEINS; GENES, FUNGAL; MEIOSIS; MUTAGENESIS; PHENOTYPE; PROTEIN STRUCTURE, TERTIARY; RECOMBINATION, GENETIC; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS; TWO-HYBRID SYSTEM TECHNIQUES;

EUKARYOTA; FUNGI; SACCHAROMYCES CEREVISIAE;

EID: 0037306175     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.23.3.873-886.2003     Document Type: Article

References (73)

1. Alani, E. 1996. The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs. Mol. Cell. Biol. 16:5604-5615.
2. Alani, E., R. A. G. Reenan, and R. D. Kolodner. 1994. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics 137:19-39.
3. Allers, T., and M. Lichten. 2001. Intermediates of yeast meiotic recombination contain heteroduplex DNA. Mol. Cell 8:225-231.
4. Allers, T., and M. Lichten. 2001. Differential timing and control of noncross-over and crossover recombination during meiosis. Cell 106:47-57.
5. Amin, N. S., M. N. Nguyen, S. Oh, and R. D. Kolodner. 2001. exol-Dependent mutator mutations: model system for studying functional interactions in mismatch repair. Mol. Cell. Biol. 21:5142-5155.
6. Argueso, J. L., D. Smith, J. Yi, M. Waase, S. Sarin, and E. Alani. 2002. Analysis of conditional mutations in the Saccharomyces cerevisiae MLH1 gene in mismatch repair and in meiotic crossing over. Genetics 160:909-921.
7. Aronshtam, A., and M. G. Marinus. 1996. Dominant negative mutator mutations in the mutL gene of Escherichia coli. Nucleic Acids Res. 24:2498-2504.
8. Ban, C., and W. Yang. 1998. Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis. Cell 95:541-552.
9. Ban, C., M. Junop, and W. Yang. 1999. Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair. Cell 97:85-97.
10. Borts, R. H., S. R. Chamhers, and M. F. Abdullah. 2000. The many faces of mismatch repair in meiosis. Mutat. Res. 451:129-150.
11. Bowers, J., P. T. Tran, R. M. Liskay, and E. Alani. 2000. Analysis of yeast MSH2-MSH6 suggests that the initiation of mismatch repair can be separated into discrete steps. J. Mol. Biol. 302:327-338.
12. Bowers, J., P. T. Tran, A. Joshi, R. M. Liskay, and E. Alani. 2001. MSH-MLH complexes formed at a DNA mismatch are disrupted by the PCNA sliding clamp. J. Mol. Biol. 306:957-968.
13. Buermeyer, A. B., S. M. Deschenes, S. M. Baker, and R. M. Liskay. 1999. Mammalian DNA mismatch repair. Annu. Rev. Genet. 33:533-564.
14. Christianson, T. W., R. S. Sikorski, M. Dante, J. H. Shero, and P. Hieter. 1992. Multifunctional yeast high-copy-number shuttle vectors. Gene 110:119-122.
15. Detloff, P., J. Sieber, and T. D. Petes. 1991. Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 11:737-745.
16. Detloff, P., M. A. White, and T. D. Petes. 1992. Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cereviae. Genetics 132:113-123.
17. Ellison, A. R., J. Lofing, and G. A. Bitter. 2001. Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae. Hum. Mol Genet. 10:1889-1900.
18. Flores-Rozas, H., and R. D. Kolodner. 1998. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Proc. Natl. Acad. Sci. USA 95:12404-12409.
19. Fogel, S., R. Mortimer, K. Lusnak, and F. Tavares. 1978. Meiotic gene conversion: a signal of the basic recombination event in yeast. Cold Spring Harbor Symp. Quant. Biol. 43:1325-1341.
20. Fogel, S., R. K. Mortimer, and K. Lusnak. 1981. Mechanisms of meiotic gene conversion, or "wanderings on a foreign strand," p. 289-339. In J. N. Strathern, E. W. Jones, and J. R. Broach (ed.), The molecular biology of the yeast Saccharomyces. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
21. Habraken, Y., P. Sung, L. Prakash, and S. Prakash. 1998. ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes. J. Biol. Chem. 273:9837-9841.
22. Hall, M. C., J. R. Jordan, and S. W. Matson. 1998. Evidence for a physical interaction between the Escherichia coli methyl-directed mismatch repair proteins MutL and UvrD. EMBO J. 17:1535-1541.
23. Hall, M. C., and S. W. Matson. 1999. The Escherichia coli MutL protein physically interacts with MutH and stimulates the MutH-associated endonuclease activity. J. Biol. Chem. 274:1306-1312.
24. Hall, M. C., and T. A. Kunkel. 2001. Purification of eukaryotic MutL homologs from Saccharomyces cerevisiae with self-affinity technology. Protein Expr. Purif. 21:333-342.
25. Hall, M. C., H, Wang, D. A. Erie, and T. A. Kunkel. 2001. High affinity cooperative DNA binding by the yeast Mlh1-Pms1 heterodimer. J. Mol. Biol. 312:637-647.
26. Hall, M. C., P. V. Shcherbakova, and T. A. Kunkel. 2002. Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal domains of the yeast Mlh1 and Pms1 proteins. J. Biol. Chem. 277:3673-3679.
27. Harfe, B. D., B. K. Minesinger, and S. Jinks-Robertson. 2000. Discrete in vivo roles for the MutL homologs Mlh2p and Mlh3p in the removal of frameshift intermediates in budding yeast. Curr. Biol. 10:145-148.
28. Henderson, S. T., and T. D. Petes. 1992. Instability of simple sequence DNA in Saccharomyces cerevisiae. Mol. Cell. Biol. 12:2749-2757.
29. Hillers, K. J., and F. W. Stahl, 1999. The conversion gradient at HIS4 of Saccharomyces cerevisiae. I. Heteroduplex rejection and restoration of Mendelian segregation. Genetics 153:555-572.
30. a. Hoffmann, E. R., P. V. Shcherbakova, T. A. Kunkel, and R. H. Borts. MLH1 mutations differentially affect meiotic functions in Saccharomyces cerevisiae. Genetics, in press.
31. Hollingsworth, N. M., L. Ponte, and C. Halsey. 1995. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 9:1728-1739.
32. Hunter, N., and N. Kleckner. 2001. The single-end invasion: an asymmetric intermediate at the double-strand break to double-Holliday junction transition of meiotic recombination. Cell 106:59-70.
33. Hunter, N., and R. H. Borts. 1997. Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Genes Dev. 11:1573-1582.
34. Jones, D. T. 1999. Protein secondary structure prediction based on position-specific scoring matrices. J. Mol. Biol. 292:195-202.
35. Khazanehdari, K. A., and R. H. Borts. 2000. EXO1 and MSH4 differentially affect crossing-over and segregation. Chromosoma 109:94-102.
36. Kirkpatrick, D. T., J. R. Ferguson, T. D. Petes, and L. S. Symington. 2000. Decreased meiotic intergenic recombination and increased meiosis I non-disjunction in exo1 mutants of Saccharomyces cerevisiae. Genetics 156:1549-1557.
37. Kolodner, R. D., and G. T. Marsischky. 1999. Eukaryotic DNA mismatch repair. Curr. Opin. Genet. Dev. 9:89-96.
38. Langland, G., J. Kordich, J. Creaney, K. Heppner Goss, K. Lillard-Wetherell, K. Bebenek, T. A. Kunkel, and J. Groden. 2001. The BLM helicase interacts with hMLH1 but is not required for DNA mismatch repair. J. Biol. Chem. 276:30031-30035.
39. Lea, D. E., and C. A. Coulson. 1949. The distribution of the numbers of mutants in bacterial populations. J. Genet. 49:264-285.
40. Lissouba, P., J. Mouseau, G. Rizet, and J. L. Rossignol. 1962. Fine structure of genes in the ascomycete Ascobolus immersus. Adv. Genet. 11:343-380.
41. Marti, T. M., C. Kunz, and O. Fleck. 2002. DNA mismatch repair and mutation avoidance pathways. J. Cell Physiol. 191:28-41.
42. Mortimer, R., and S. Fogel. 1974. Genetical interference and gene conversion, p. 263-275 In R. Grell (ed.), Mechanisms in recombination. Plenum Press, New York, N.Y.
43. Nicolas, A., D. Treco, N. P. Schultes, and J. W. Szostak. 1989. An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae. Nature 338:35-39.
44. Novak, J. E., P. B. Ross-Macdonald, and G. S. Roeder. 2001. The budding yeast Msh4 protein functions in chromosome synapsis and the regulation of crossover distribution. Genetics 158:1013-1025.
45. Nystrom-Lahti, M., C. Perrera, M. Raschle, E. Panyushkina-Seiler, G. Marra, A. Curci, B. Quaresima, F. Costanzo, M. D'Urso, S. Venuta, and J. Jiricny. 2002. Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer. Genes Chromosomes Cancer 33:160-167.
46. Pang, Q., T. A. Prolla, and R. M. Liskay. 1997. Functional domains of the Saccharomyces cerevisiae Mlh1p and Pms1p DNA mismatch repair proteins and their relevance to human hereditary nonpolyposis colorectal cancerassociated mutations. Mol. Cell. Biol. 17:4465-4473.
47. Papazian, H. P. 1952. The analysis of tetrad data. Genetics 37:175-188.
48. Paques, F., and J. E. Haber. 1999. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63:349-404.
49. Pedrazzi, G., C. Perrera, H. Blaser, P. Kuster, G. Marra, S. L. Davies, G. H. Ryu, R. Freire, I. D. Hickson, J. Jiricny, and I. Stagljar. 2001. Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1. Nucleic Acids Res. 29:4378-4386.
50. Perkins, D. D. 1949. Biochemical mutants in the smut fungus Ustilago maydis. Genetics 34:607-626.
51. Raschle, M., P. Dufner, G. Marra, and J. Jiricny. 2002. Mutations within the hMLH1 and hPMS2 subunits of the human MutLa mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSa. J. Biol. Chem. 277:21810-21820.
52. Reenan, R. A., and R. D. Kolodner. 1992. Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Genetics 132:975-985.
53. Rocco, V., B. de Massy, and A. Nicolas, 1992. The Saccharomyces cerevisiae ARG4 initiator of meiotic gene conversion and its associated double-strand DNA breaks can be inhibited by transcriptional interference. Proc. Natl. Acad. Sci. USA 89:12068-12072.
54. Rose, M. D., F. Winston, and P. Hieter. 1990. Methods in yeast genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
55. Ross-Macdonald, P., and G. S. Roeder. 1994. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell 79:1069-1080.
56. Rossignol, J. L., A. Nicolas, H. Hamza, and T. Langin. 1984. Origins of gene conversion and reciprocal exchange in Ascobolus. Cold Spring Harbor Symp. Quant. Biol. 49:13-21.
57. Santucci-Darmanin, S., D. Walpita, F. Lespinasse, C. Desnuelle, T. Ashley, and V. Paquis-Flucklinger, 2000. MSH4 acts in conjunction with MLH1 during mammalian meiosis. FASEB J. 14:1539-1547.
58. Shcherbakova, P. V., M. C. Hall, M. S. Lewis, S. E. Bennett, K. J. Martin, P. R. Bushel, C. A. Afshari, and T. A. Kunkel. 2001. Inactivation of DNA mismatch repair by increased expression of yeast MLHI. Mol. Cell. Biol. 21:940-951.
59. Sia, E. A., M. Dominska, L. Stefanovic, and T. D. Petes. 2001. Isolation and characterization of point mutations in mismatch repair genes that destabilize microsatel[ites in yeast. Mol. Cell. Biol. 21:8157-8167.
60. Sokolsky, T., and E. Alani. 2000. EXO1 and MSH6 are high-copy suppressors of conditional mutations in the MSH2 mismatch repair gene of Saccharomyces cerevisiae. Genetics 155:589-599.
61. Spampinato, C., and P. Modrich. 2000. The MutL ATPase is required for mismatch repair. J. Biol. Chem. 275:9863-9869.
62. Sun, H., D. Treco, N. P. Schultes, and J. W. Szostak. 1989. Double-strand breaks at an initiation site for meiotic gene conversion. Nature 338:87-90.
63. Tishkoff, D. X., A. L. Boerger, P. Bertrand, N. Filosi, G. M. Gaida, M. F. Kane, and R. D. Kolodner. 1997. Identification and characterization of Saccharomyces cerevisiae EXO1, a gene encoding an exonuclease that interacts with MSH2. Proc. Natl. Acad. Sci. USA 94:7487-7492.
64. Tomer, G., A. B. Buermeyer, M. M. Nguyen, and R. M. Liskay. 2002. Contribution of human Mlh1 and Pms2 ATPase activities to DNA mismatch repair. J. Biol. Chem. 277:21801-21809.
65. Tran, P. T., and R. M. Liskay. 2000. Functional studies on the candidate ATPase domains of Saccharomyces cerevisiae MutLa. Mol. Cell. Biol. 20:6390-6398.
66. Tran, P. T., J. A. Simon, and R. M. Liskay. 2001. Interactions of Exo1p with components of MutLa in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 98:9760-9765.
67. Tsubouchi, H., and H. Ogawa. 2000. Exo1 roles for repair of DNA doublestrand breaks and meiotic crossing over in Saccharomyces cerevisiae. Mol. Biol. Cell 11:2221-2233.
68. Vedel, M., and A. Nicolas. 1999. CYS3, a hot spot of meiotic recombination in Saccharomyces cerevisiae: effects of heterozygosity and mismatch repair functions on gene conversion and recombination intermediates. Genetics 151:1245-1259.
69. Vojtek, A. B., S. M. Hollenberg, and J. A. Cooper. 1993. Mammalian ras interacts directly with the serine/threonine kinase Raf. Cell 74:205-214.
70. Wach, A., A. Brachat, R. Pohlmann, and P. Philippsen. 1994. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10:1793-1808.
71. Wang, T. F., N. Kleckner, and N. Hunter. 1999. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proc. Natl. Acad. Sci. USA 96:13914-13919.
72. White, J. H., K. Lusnak, and S. Fogel. 1985. Mismatch-specific postmeiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate. Nature 315:350-352.
73. Woods, L. M., C. A. Hodges, E. Baart, S. M. Baker, R. M. Liskay, and P. A. Hunt. 1999. Chromosomal influence on meiotic spindle assembly: abnormal meiosis 1 in female Mlh1 mutant mice. J. Cell Biol. 145:1395-1406.