Abstract
The Saccharomyces cerevisiae homologs of the bacterial mismatch repair proteins MutS and MutL correct replication errors and prevent recombination between homeologous (nonidentical) sequences. Previously, we demonstrated that Msh2p, Msh3p, and Pms1p regulate recombination between 91% identical inverted repeats, and here use the same substrates to show that Mlh1p and Msh6p have important antirecombination roles. In addition, substrates containing defined types of mismatches (base-base mismatches; 1-, 4-, or 12-nt insertion/deletion loops; or 18-nt palindromes) were used to examine recognition of these mismatches in mitotic recombination intermediates. Msh2p was required for recognition of all types of mismatches, whereas Msh6p recognized only base-base mismatches and 1-nt insertion/deletion loops. Msh3p was involved in recognition of the palindrome and all loops, but also had an unexpected antirecombination role when the potential heteroduplex contained only base-base mismatches. In contrast to their similar antimutator roles, Pms1p consistently inhibited recombination to a lesser degree than did Msh2p. In addition to the yeast MutS and MutL homologs, the exonuclease Exo1p and the nucleotide excision repair proteins Rad1p and Rad10p were found to have roles in inhibiting recombination between mismatched substrates.
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- Abdulkarim F., Hughes D. Homologous recombination between the tuf genes of Salmonella typhimurium. J Mol Biol. 1996 Jul 26;260(4):506–522. doi: 10.1006/jmbi.1996.0418. [DOI] [PubMed] [Google Scholar]
- Alani E., Cao L., Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. doi: 10.1534/genetics.112.541.test. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alani E., Lee S., Kane M. F., Griffith J., Kolodner R. D. Saccharomyces cerevisiae MSH2, a mispaired base recognition protein, also recognizes Holliday junctions in DNA. J Mol Biol. 1997 Jan 24;265(3):289–301. doi: 10.1006/jmbi.1996.0743. [DOI] [PubMed] [Google Scholar]
- Bardwell L., Cooper A. J., Friedberg E. C. Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro. Mol Cell Biol. 1992 Jul;12(7):3041–3049. doi: 10.1128/mcb.12.7.3041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bertrand P., Tishkoff D. X., Filosi N., Dasgupta R., Kolodner R. D. Physical interaction between components of DNA mismatch repair and nucleotide excision repair. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14278–14283. doi: 10.1073/pnas.95.24.14278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chambers S. P., Prior S. E., Barstow D. A., Minton N. P. The pMTL nic- cloning vectors. I. Improved pUC polylinker regions to facilitate the use of sonicated DNA for nucleotide sequencing. Gene. 1988 Aug 15;68(1):139–149. doi: 10.1016/0378-1119(88)90606-3. [DOI] [PubMed] [Google Scholar]
- Chen W., Jinks-Robertson S. The role of the mismatch repair machinery in regulating mitotic and meiotic recombination between diverged sequences in yeast. Genetics. 1999 Apr;151(4):1299–1313. doi: 10.1093/genetics/151.4.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ciotta C., Ceccotti S., Aquilina G., Humbert O., Palombo F., Jiricny J., Bignami M. Increased somatic recombination in methylation tolerant human cells with defective DNA mismatch repair. J Mol Biol. 1998 Mar 6;276(4):705–719. doi: 10.1006/jmbi.1997.1559. [DOI] [PubMed] [Google Scholar]
- Datta A., Adjiri A., New L., Crouse G. F., Jinks Robertson S. Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccaromyces cerevisiae. Mol Cell Biol. 1996 Mar;16(3):1085–1093. doi: 10.1128/mcb.16.3.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Datta A., Jinks-Robertson S. Association of increased spontaneous mutation rates with high levels of transcription in yeast. Science. 1995 Jun 16;268(5217):1616–1619. doi: 10.1126/science.7777859. [DOI] [PubMed] [Google Scholar]
- Davies A. A., Friedberg E. C., Tomkinson A. E., Wood R. D., West S. C. Role of the Rad1 and Rad10 proteins in nucleotide excision repair and recombination. J Biol Chem. 1995 Oct 20;270(42):24638–24641. doi: 10.1074/jbc.270.42.24638. [DOI] [PubMed] [Google Scholar]
- Earley M. C., Crouse G. F. Selectable cassettes for simplified construction of yeast gene disruption vectors. Gene. 1996 Feb 22;169(1):111–113. doi: 10.1016/0378-1119(95)00805-5. [DOI] [PubMed] [Google Scholar]
- Earley M. C., Crouse G. F. The role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15487–15491. doi: 10.1073/pnas.95.26.15487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fiorentini P., Huang K. N., Tishkoff D. X., Kolodner R. D., Symington L. S. Exonuclease I of Saccharomyces cerevisiae functions in mitotic recombination in vivo and in vitro. Mol Cell Biol. 1997 May;17(5):2764–2773. doi: 10.1128/mcb.17.5.2764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleck O., Lehmann E., Schär P., Kohli J. Involvement of nucleotide-excision repair in msh2 pms1-independent mismatch repair. Nat Genet. 1999 Mar;21(3):314–317. doi: 10.1038/6838. [DOI] [PubMed] [Google Scholar]
- Flores-Rozas H., Kolodner R. D. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12404–12409. doi: 10.1073/pnas.95.21.12404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene C. N., Jinks-Robertson S. Frameshift intermediates in homopolymer runs are removed efficiently by yeast mismatch repair proteins. Mol Cell Biol. 1997 May;17(5):2844–2850. doi: 10.1128/mcb.17.5.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Habraken Y., Sung P., Prakash L., Prakash S. Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3. Curr Biol. 1996 Sep 1;6(9):1185–1187. doi: 10.1016/s0960-9822(02)70686-6. [DOI] [PubMed] [Google Scholar]
- Harfe B. D., Jinks-Robertson S. Removal of frameshift intermediates by mismatch repair proteins in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Jul;19(7):4766–4773. doi: 10.1128/mcb.19.7.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higgins D. R., Prakash S., Reynolds P., Prakash L. Molecular cloning and characterization of the RAD1 gene of Saccharomyces cerevisiae. Gene. 1983 Dec;26(2-3):119–126. doi: 10.1016/0378-1119(83)90181-6. [DOI] [PubMed] [Google Scholar]
- Hollingsworth N. M., Ponte L., Halsey C. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 1995 Jul 15;9(14):1728–1739. doi: 10.1101/gad.9.14.1728. [DOI] [PubMed] [Google Scholar]
- Humbert O., Prudhomme M., Hakenbeck R., Dowson C. G., Claverys J. P. Homeologous recombination and mismatch repair during transformation in Streptococcus pneumoniae: saturation of the Hex mismatch repair system. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9052–9056. doi: 10.1073/pnas.92.20.9052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Johnson R. E., Kovvali G. K., Guzder S. N., Amin N. S., Holm C., Habraken Y., Sung P., Prakash L., Prakash S. Evidence for involvement of yeast proliferating cell nuclear antigen in DNA mismatch repair. J Biol Chem. 1996 Nov 8;271(45):27987–27990. doi: 10.1074/jbc.271.45.27987. [DOI] [PubMed] [Google Scholar]
- Johnson R. E., Kovvali G. K., Prakash L., Prakash S. Requirement of the yeast MSH3 and MSH6 genes for MSH2-dependent genomic stability. J Biol Chem. 1996 Mar 29;271(13):7285–7288. doi: 10.1074/jbc.271.13.7285. [DOI] [PubMed] [Google Scholar]
- Kirkpatrick D. T., Petes T. D. Repair of DNA loops involves DNA-mismatch and nucleotide-excision repair proteins. Nature. 1997 Jun 26;387(6636):929–931. doi: 10.1038/43225. [DOI] [PubMed] [Google Scholar]
- Kolodner R. Biochemistry and genetics of eukaryotic mismatch repair. Genes Dev. 1996 Jun 15;10(12):1433–1442. doi: 10.1101/gad.10.12.1433. [DOI] [PubMed] [Google Scholar]
- Kramer W., Fartmann B., Ringbeck E. C. Transcription of mutS and mutL-homologous genes in Saccharomyces cerevisiae during the cell cycle. Mol Gen Genet. 1996 Sep 13;252(3):275–283. doi: 10.1007/BF02173773. [DOI] [PubMed] [Google Scholar]
- Lühr B., Scheller J., Meyer P., Kramer W. Analysis of in vivo correction of defined mismatches in the DNA mismatch repair mutants msh2, msh3 and msh6 of Saccharomyces cerevisiae. Mol Gen Genet. 1998 Feb;257(3):362–367. doi: 10.1007/s004380050658. [DOI] [PubMed] [Google Scholar]
- Majewski J., Cohan F. M. The effect of mismatch repair and heteroduplex formation on sexual isolation in Bacillus. Genetics. 1998 Jan;148(1):13–18. doi: 10.1093/genetics/148.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marsh J. L., Erfle M., Wykes E. J. The pIC plasmid and phage vectors with versatile cloning sites for recombinant selection by insertional inactivation. Gene. 1984 Dec;32(3):481–485. doi: 10.1016/0378-1119(84)90022-2. [DOI] [PubMed] [Google Scholar]
- Marsischky G. T., Filosi N., Kane M. F., Kolodner R. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev. 1996 Feb 15;10(4):407–420. doi: 10.1101/gad.10.4.407. [DOI] [PubMed] [Google Scholar]
- Modrich P., Lahue R. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem. 1996;65:101–133. doi: 10.1146/annurev.bi.65.070196.000533. [DOI] [PubMed] [Google Scholar]
- Nag D. K., Petes T. D. Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae. Genetics. 1991 Nov;129(3):669–673. doi: 10.1093/genetics/129.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Negritto M. T., Wu X., Kuo T., Chu S., Bailis A. M. Influence of DNA sequence identity on efficiency of targeted gene replacement. Mol Cell Biol. 1997 Jan;17(1):278–286. doi: 10.1128/mcb.17.1.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prolla T. A., Christie D. M., Liskay R. M. Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene. Mol Cell Biol. 1994 Jan;14(1):407–415. doi: 10.1128/mcb.14.1.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prolla T. A., Pang Q., Alani E., Kolodner R. D., Liskay R. M. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994 Aug 19;265(5175):1091–1093. doi: 10.1126/science.8066446. [DOI] [PubMed] [Google Scholar]
- Rayssiguier C., Thaler D. S., Radman M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature. 1989 Nov 23;342(6248):396–401. doi: 10.1038/342396a0. [DOI] [PubMed] [Google Scholar]
- Ross-Macdonald P., Roeder G. S. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell. 1994 Dec 16;79(6):1069–1080. doi: 10.1016/0092-8674(94)90037-x. [DOI] [PubMed] [Google Scholar]
- Saparbaev M., Prakash L., Prakash S. Requirement of mismatch repair genes MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination in Saccharomyces cerevisiae. Genetics. 1996 Mar;142(3):727–736. doi: 10.1093/genetics/142.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sekelsky J. J., McKim K. S., Chin G. M., Hawley R. S. The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics. 1995 Oct;141(2):619–627. doi: 10.1093/genetics/141.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selva E. M., New L., Crouse G. F., Lahue R. S. Mismatch correction acts as a barrier to homeologous recombination in Saccharomyces cerevisiae. Genetics. 1995 Mar;139(3):1175–1188. doi: 10.1093/genetics/139.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sia E. A., Kokoska R. J., Dominska M., Greenwell P., Petes T. D. Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes. Mol Cell Biol. 1997 May;17(5):2851–2858. doi: 10.1128/mcb.17.5.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siede W., Friedberg A. S., Friedberg E. C. Evidence that the Rad1 and Rad10 proteins of Saccharomyces cerevisiae participate as a complex in nucleotide excision repair of UV radiation damage. J Bacteriol. 1993 Oct;175(19):6345–6347. doi: 10.1128/jb.175.19.6345-6347.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugawara N., Pâques F., Colaiácovo M., Haber J. E. Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9214–9219. doi: 10.1073/pnas.94.17.9214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sweder K. S. Nucleotide excision repair in yeast. Curr Genet. 1994 Dec;27(1):1–16. doi: 10.1007/BF00326572. [DOI] [PubMed] [Google Scholar]
- Tishkoff D. X., Boerger A. L., Bertrand P., Filosi N., Gaida G. M., Kane M. F., Kolodner R. D. Identification and characterization of Saccharomyces cerevisiae EXO1, a gene encoding an exonuclease that interacts with MSH2. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7487–7492. doi: 10.1073/pnas.94.14.7487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tran H. T., Gordenin D. A., Resnick M. A. The 3'-->5' exonucleases of DNA polymerases delta and epsilon and the 5'-->3' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Mar;19(3):2000–2007. doi: 10.1128/mcb.19.3.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Umar A., Boyer J. C., Kunkel T. A. DNA loop repair by human cell extracts. Science. 1994 Nov 4;266(5186):814–816. doi: 10.1126/science.7973637. [DOI] [PubMed] [Google Scholar]
- Umar A., Buermeyer A. B., Simon J. A., Thomas D. C., Clark A. B., Liskay R. M., Kunkel T. A. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell. 1996 Oct 4;87(1):65–73. doi: 10.1016/s0092-8674(00)81323-9. [DOI] [PubMed] [Google Scholar]
- Umar A., Risinger J. I., Glaab W. E., Tindall K. R., Barrett J. C., Kunkel T. A. Functional overlap in mismatch repair by human MSH3 and MSH6. Genetics. 1998 Apr;148(4):1637–1646. doi: 10.1093/genetics/148.4.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wach A., Brachat A., Pöhlmann R., Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. doi: 10.1002/yea.320101310. [DOI] [PubMed] [Google Scholar]
- Weiss W. A., Friedberg E. C. Molecular cloning and characterization of the yeast RAD10 gene and expression of RAD10 protein in E. coli. EMBO J. 1985 Jun;4(6):1575–1582. doi: 10.1002/j.1460-2075.1985.tb03819.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zahrt T. C., Maloy S. Barriers to recombination between closely related bacteria: MutS and RecBCD inhibit recombination between Salmonella typhimurium and Salmonella typhi. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9786–9791. doi: 10.1073/pnas.94.18.9786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Wind N., Dekker M., Berns A., Radman M., te Riele H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995 Jul 28;82(2):321–330. doi: 10.1016/0092-8674(95)90319-4. [DOI] [PubMed] [Google Scholar]