Mechanisms of dinucleotide repeat instability in Escherichia coli.
Abstract
The high level of polymorphism of microsatellites has been used for a variety of purposes such as positional cloning of genes associated with diseases, forensic medicine, and phylogenetic studies. The discovery that microsatellites are associated with human diseases, not only as markers of risk but also directly in disease pathogenesis, has triggered a renewed interest in understanding the mechanism of their instability. In this work we have investigated the role of DNA replication, long patch mismatch repair, and transcription on the genetic instability of all possible combinations of dinucleotide repeats in Escherichia coli. We show that the (GpC) and (ApT) self-complementary sequence repeats are the most unstable and that the mode of replication plays an important role in their instability. We also found that long patch mismatch repair is involved in avoiding both short deletion and expansion events and also in instabilities resulting from the processing of bulges of 6 to 8 bp for the (GpT/ApC)- and (ApG/CpT)- containing repeats. For each dinucleotide sequence repeat, we propose models for instability that involve the possible participation of unusual secondary structures.
Full Text
The Full Text of this article is available as a PDF (199K).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med. 1995 Dec 1;182(6):1985–1996.[PMC free article] [PubMed] [Google Scholar]
- Gordenin DA, Kunkel TA, Resnick MA. Repeat expansion--all in a flap? Nat Genet. 1997 Jun;16(2):116–118. [PubMed] [Google Scholar]
- Hanvey JC, Shimizu M, Wells RD. Intramolecular DNA triplexes in supercoiled plasmids. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6292–6296.[PMC free article] [PubMed] [Google Scholar]
- Htun H, Dahlberg JE. Topology and formation of triple-stranded H-DNA. Science. 1989 Mar 24;243(4898):1571–1576. [PubMed] [Google Scholar]
- Jackson AL, Newcomb TG, Loeb LA. Origin of multiple mutations in human cancers. Drug Metab Rev. 1998 May;30(2):285–304. [PubMed] [Google Scholar]
- Jaworski A, Blaho JA, Larson JE, Shimizu M, Wells RD. Tetracycline promoter mutations decrease non-B DNA structural transitions, negative linking differences and deletions in recombinant plasmids in Escherichia coli. J Mol Biol. 1989 Jun 5;207(3):513–526. [PubMed] [Google Scholar]
- Jiricny J. Replication errors: cha(lle)nging the genome. EMBO J. 1998 Nov 16;17(22):6427–6436.[PMC free article] [PubMed] [Google Scholar]
- Johnson RE, Kovvali GK, Guzder SN, Amin NS, 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. [PubMed] [Google Scholar]
- Kramer B, Kramer W, Fritz HJ. 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. [PubMed] [Google Scholar]
- Kunkel TA. Misalignment-mediated DNA synthesis errors. Biochemistry. 1990 Sep 4;29(35):8003–8011. [PubMed] [Google Scholar]
- Levinson G, Gutman GA. High frequencies of short frameshifts in poly-CA/TG tandem repeats borne by bacteriophage M13 in Escherichia coli K-12. Nucleic Acids Res. 1987 Jul 10;15(13):5323–5338.[PMC free article] [PubMed] [Google Scholar]
- Loeb LA. Cancer cells exhibit a mutator phenotype. Adv Cancer Res. 1998;72:25–56. [PubMed] [Google Scholar]
- McMurray CT. Mechanisms of DNA expansion. Chromosoma. 1995 Oct;104(1):2–13. [PubMed] [Google Scholar]
- Panyutin IG, Wells RD. Nodule DNA in the (GA)37.(CT)37 insert in superhelical plasmids. J Biol Chem. 1992 Mar 15;267(8):5495–5501. [PubMed] [Google Scholar]
- Papanicolaou C, Ripley LS. Polymerase-specific differences in the DNA intermediates of frameshift mutagenesis. In vitro synthesis errors of Escherichia coli DNA polymerase I and its large fragment derivative. J Mol Biol. 1989 May 20;207(2):335–353. [PubMed] [Google Scholar]
- Papanicolaou C, Ripley LS. An in vitro approach to identifying specificity determinants of mutagenesis mediated by DNA misalignments. J Mol Biol. 1991 Oct 5;221(3):805–821. [PubMed] [Google Scholar]
- Pearson CE, Sinden RR. Alternative structures in duplex DNA formed within the trinucleotide repeats of the myotonic dystrophy and fragile X loci. Biochemistry. 1996 Apr 16;35(15):5041–5053. [PubMed] [Google Scholar]
- Backman K, Betlach M, Boyer HW, Yanofsky S. Genetic and physical studies on the replication of ColE1-type plasmids. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 1):69–76. [PubMed] [Google Scholar]
- Ripley LS. Frameshift mutation: determinants of specificity. Annu Rev Genet. 1990;24:189–213. [PubMed] [Google Scholar]
- Bichara M, Schumacher S, Fuchs RP. Genetic instability within monotonous runs of CpG sequences in Escherichia coli. Genetics. 1995 Jul;140(3):897–907.[PMC free article] [PubMed] [Google Scholar]
- Bowater RP, Jaworski A, Larson JE, Parniewski P, Wells RD. Transcription increases the deletion frequency of long CTG.CAG triplet repeats from plasmids in Escherichia coli. Nucleic Acids Res. 1997 Jul 15;25(14):2861–2868.[PMC free article] [PubMed] [Google Scholar]
- Sia EA, Jinks-Robertson S, Petes TD. Genetic control of microsatellite stability. Mutat Res. 1997 Jan 31;383(1):61–70. [PubMed] [Google Scholar]
- Carraway M, Marinus MG. Repair of heteroduplex DNA molecules with multibase loops in Escherichia coli. J Bacteriol. 1993 Jul;175(13):3972–3980.[PMC free article] [PubMed] [Google Scholar]
- Strand M, Earley MC, Crouse GF, Petes TD. Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10418–10421.[PMC free article] [PubMed] [Google Scholar]
- Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzaghi E, Inouye M. Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harb Symp Quant Biol. 1966;31:77–84. [PubMed] [Google Scholar]
- Wells RD. Molecular basis of genetic instability of triplet repeats. J Biol Chem. 1996 Feb 9;271(6):2875–2878. [PubMed] [Google Scholar]
- Wells RD, Bacolla A, Bowater RP. Instabilities of triplet repeats: factors and mechanisms. Results Probl Cell Differ. 1998;21:133–165. [PubMed] [Google Scholar]
- Wierdl M, Greene CN, Datta A, Jinks-Robertson S, Petes TD. Destabilization of simple repetitive DNA sequences by transcription in yeast. Genetics. 1996 Jun;143(2):713–721.[PMC free article] [PubMed] [Google Scholar]
- Wooster R, Cleton-Jansen AM, Collins N, Mangion J, Cornelis RS, Cooper CS, Gusterson BA, Ponder BA, von Deimling A, Wiestler OD, et al. Instability of short tandem repeats (microsatellites) in human cancers. Nat Genet. 1994 Feb;6(2):152–156. [PubMed] [Google Scholar]
- Yang Y, Masker W. Instability of repeated dinucleotides in bacteriophage T7 genomes. Mutat Res. 1996 Jul 5;354(1):113–127. [PubMed] [Google Scholar]
- Weaver DT, DePamphilis ML. The role of palindromic and non-palindromic sequences in arresting DNA synthesis in vitro and in vivo. J Mol Biol. 1984 Dec 25;180(4):961–986. [PubMed] [Google Scholar]
Abstract
The high level of polymorphism of microsatellites has been used for a variety of purposes such as positional cloning of genes associated with diseases, forensic medicine, and phylogenetic studies. The discovery that microsatellites are associated with human diseases, not only as markers of risk but also directly in disease pathogenesis, has triggered a renewed interest in understanding the mechanism of their instability. In this work we have investigated the role of DNA replication, long patch mismatch repair, and transcription on the genetic instability of all possible combinations of dinucleotide repeats in Escherichia coli. We show that the (GpC) and (ApT) self-complementary sequence repeats are the most unstable and that the mode of replication plays an important role in their instability. We also found that long patch mismatch repair is involved in avoiding both short deletion and expansion events and also in instabilities resulting from the processing of bulges of 6 to 8 bp for the (GpT/ApC)- and (ApG/CpT)- containing repeats. For each dinucleotide sequence repeat, we propose models for instability that involve the possible participation of unusual secondary structures.