Abstract
An activity in nuclear extracts of S.cerevisiae binds specifically to heteroduplexes containing four to nine extra bases in one strand. The specificity of this activity (IMR, for insertion mismatch recognition) in band shift assays was confirmed by competition experiments. IMR is biochemically and genetically distinct from the MSH2 dependent, single base mismatch binding activity. The two activities migrate differently during electrophoresis, they are differentially competable and their spectra of mispair binding are distinct. Furthermore, IMR activity is observed in extracts from an msh2- msh3- msh4- strain. IMR exhibits specificity for insertion mispairs in two different sequence contexts. Binding is influenced by the structure of the mismatch since an insertion with a hairpin configuration is not recognized by this activity. IMR does not result from single-strand binding because single-stranded probes to not yield IMR complex and single-stranded competitors are unable to displace insertion heteroduplexes from the complex. Similar results with intrinsically bent duplexes make it unlikely that recognition is conferred by a bend alone. Heteroduplexes bound by IMR do not contain any obvious damage. These findings are consistent with the idea that yeast contains a distinct recognition factor, IMR that is specific for insertion/deletion mismatches.
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Selected References
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- Alani E., Chi N. W., Kolodner R. The Saccharomyces cerevisiae Msh2 protein specifically binds to duplex oligonucleotides containing mismatched DNA base pairs and insertions. Genes Dev. 1995 Jan 15;9(2):234–247. doi: 10.1101/gad.9.2.234. [DOI] [PubMed] [Google Scholar]
- Alani E., Reenan R. A., Kolodner R. D. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics. 1994 May;137(1):19–39. doi: 10.1093/genetics/137.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bhattacharyya A., Lilley D. M. The contrasting structures of mismatched DNA sequences containing looped-out bases (bulges) and multiple mismatches (bubbles). Nucleic Acids Res. 1989 Sep 12;17(17):6821–6840. doi: 10.1093/nar/17.17.6821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Bronner C. E., Baker S. M., Morrison P. T., Warren G., Smith L. G., Lescoe M. K., Kane M., Earabino C., Lipford J., Lindblom A. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994 Mar 17;368(6468):258–261. doi: 10.1038/368258a0. [DOI] [PubMed] [Google Scholar]
- Carraway M., Marinus M. G. Repair of heteroduplex DNA molecules with multibase loops in Escherichia coli. J Bacteriol. 1993 Jul;175(13):3972–3980. doi: 10.1128/jb.175.13.3972-3980.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chi N. W., Kolodner R. D. Purification and characterization of MSH1, a yeast mitochondrial protein that binds to DNA mismatches. J Biol Chem. 1994 Nov 25;269(47):29984–29992. [PubMed] [Google Scholar]
- Drummond J. T., Li G. M., Longley M. J., Modrich P. Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science. 1995 Jun 30;268(5219):1909–1912. doi: 10.1126/science.7604264. [DOI] [PubMed] [Google Scholar]
- Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
- Gasc A. M., Garcia P., Baty D., Sicard A. M. Mismatch repair during pneumococcal transformation of small deletions produced by site-directed mutagenesis. Mol Gen Genet. 1987 Dec;210(2):369–372. doi: 10.1007/BF00325708. [DOI] [PubMed] [Google Scholar]
- Haran T. E., Kahn J. D., Crothers D. M. Sequence elements responsible for DNA curvature. J Mol Biol. 1994 Nov 25;244(2):135–143. doi: 10.1006/jmbi.1994.1713. [DOI] [PubMed] [Google Scholar]
- Henderson S. T., Petes T. D. Instability of simple sequence DNA in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Jun;12(6):2749–2757. doi: 10.1128/mcb.12.6.2749. [DOI] [PMC free article] [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]
- Hsieh C. H., Griffith J. D. Deletions of bases in one strand of duplex DNA, in contrast to single-base mismatches, produce highly kinked molecules: possible relevance to the folding of single-stranded nucleic acids. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4833–4837. doi: 10.1073/pnas.86.13.4833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kolodner R. D. Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends Biochem Sci. 1995 Oct;20(10):397–401. doi: 10.1016/s0968-0004(00)89087-8. [DOI] [PubMed] [Google Scholar]
- Koo H. S., Drak J., Rice J. A., Crothers D. M. Determination of the extent of DNA bending by an adenine-thymine tract. Biochemistry. 1990 May 1;29(17):4227–4234. doi: 10.1021/bi00469a027. [DOI] [PubMed] [Google Scholar]
- Kramer B., Kramer W., Williamson M. S., Fogel S. Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes. Mol Cell Biol. 1989 Oct;9(10):4432–4440. doi: 10.1128/mcb.9.10.4432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leach F. S., Nicolaides N. C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomäki P., Sistonen P., Aaltonen L. A., Nyström-Lahti M. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215–1225. doi: 10.1016/0092-8674(93)90330-s. [DOI] [PubMed] [Google Scholar]
- Lefèvre J. C., Mostachfi P., Gasc A. M., Guillot E., Pasta F., Sicard M. Conversion of deletions during recombination in pneumococcal transformation. Genetics. 1989 Nov;123(3):455–464. doi: 10.1093/genetics/123.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miret J. J., Milla M. G., Lahue R. S. Characterization of a DNA mismatch-binding activity in yeast extracts. J Biol Chem. 1993 Feb 15;268(5):3507–3513. [PubMed] [Google Scholar]
- Modrich P. Mechanisms and biological effects of mismatch repair. Annu Rev Genet. 1991;25:229–253. doi: 10.1146/annurev.ge.25.120191.001305. [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]
- Nag D. K., White M. A., Petes T. D. Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast. Nature. 1989 Jul 27;340(6231):318–320. doi: 10.1038/340318a0. [DOI] [PubMed] [Google Scholar]
- New L., Liu K., Crouse G. F. The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. Mol Gen Genet. 1993 May;239(1-2):97–108. doi: 10.1007/BF00281607. [DOI] [PubMed] [Google Scholar]
- Palombo F., Gallinari P., Iaccarino I., Lettieri T., Hughes M., D'Arrigo A., Truong O., Hsuan J. J., Jiricny J. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. Science. 1995 Jun 30;268(5219):1912–1914. doi: 10.1126/science.7604265. [DOI] [PubMed] [Google Scholar]
- Papadopoulos N., Nicolaides N. C., Wei Y. F., Ruben S. M., Carter K. C., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M., Adams M. D. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994 Mar 18;263(5153):1625–1629. doi: 10.1126/science.8128251. [DOI] [PubMed] [Google Scholar]
- Parker B. O., Marinus M. G. Repair of DNA heteroduplexes containing small heterologous sequences in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1730–1734. doi: 10.1073/pnas.89.5.1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parsons R., Li G. M., Longley M. J., Fang W. H., Papadopoulos N., Jen J., de la Chapelle A., Kinzler K. W., Vogelstein B., Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993 Dec 17;75(6):1227–1236. doi: 10.1016/0092-8674(93)90331-j. [DOI] [PubMed] [Google Scholar]
- Reenan R. A., Kolodner R. D. Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Genetics. 1992 Dec;132(4):975–985. doi: 10.1093/genetics/132.4.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reenan R. A., Kolodner R. D. Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. Genetics. 1992 Dec;132(4):963–973. doi: 10.1093/genetics/132.4.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rewinski C., Marinus M. G. Mutation spectrum in Escherichia coli DNA mismatch repair deficient (mutH) strain. Nucleic Acids Res. 1987 Oct 26;15(20):8205–8215. doi: 10.1093/nar/15.20.8205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosen M. A., Live D., Patel D. J. Comparative NMR study of A(n)-bulge loops in DNA duplexes: intrahelical stacking of A, A-A, and A-A-A bulge loops. Biochemistry. 1992 Apr 28;31(16):4004–4014. doi: 10.1021/bi00131a016. [DOI] [PubMed] [Google Scholar]
- Rosen M. A., Shapiro L., Patel D. J. Solution structure of a trinucleotide A-T-A bulge loop within a DNA duplex. Biochemistry. 1992 Apr 28;31(16):4015–4026. doi: 10.1021/bi00131a017. [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]
- Strand M., Prolla T. A., Liskay R. M., Petes T. D. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature. 1993 Sep 16;365(6443):274–276. doi: 10.1038/365274a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Tran H. T., Degtyareva N. P., Koloteva N. N., Sugino A., Masumoto H., Gordenin D. A., Resnick M. A. Replication slippage between distant short repeats in Saccharomyces cerevisiae depends on the direction of replication and the RAD50 and RAD52 genes. Mol Cell Biol. 1995 Oct;15(10):5607–5617. doi: 10.1128/mcb.15.10.5607. [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]
- Vincent A., Petes T. D. Mitotic and meiotic gene conversion of Ty elements and other insertions in Saccharomyces cerevisiae. Genetics. 1989 Aug;122(4):759–772. doi: 10.1093/genetics/122.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang Y. H., Griffith J. Effects of bulge composition and flanking sequence on the kinking of DNA by bulged bases. Biochemistry. 1991 Feb 5;30(5):1358–1363. doi: 10.1021/bi00219a028. [DOI] [PubMed] [Google Scholar]
- Wang Z., Wu X., Friedberg E. C. Nucleotide-excision repair of DNA in cell-free extracts of the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4907–4911. doi: 10.1073/pnas.90.11.4907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
