Mutational analyses of dinucleotide and tetranucleotide microsatellites in Escherichia coli: Influence of sequence on expansion mutagenesis

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Mutagenesis at [GT/CA]10 [TC/AG]11 and [TTCC/AAGG]9 microsatellite sequences inserted in the herpes simplex virus thymidine kinase (HSV-tk) gene was analyzed in isogenic mut(L)+ and mut(L)- Escherichia coli. In both strains, significantly more expansion than deletion mutations were observed at the [TTCC/AAGG]9 motif relative to either dinucleotide motif. As the HSV-tk coding sequence contains an endogenous [G/C]7 mononucleotide repeat and ~1000 bp of unique sequence, we were able to compare mutagenesis among various sequence motifs. We observed that the relative risk of mutation in E.coli is: [TTCC/AAGG]9 > [TTCC/AAGG]10 ~ [TC/AG]11 > unique ~ [G/C]7. The mutation frequency varied 1400- fold fold in mutL+ cells between the tetranucleotide motif and the mononucleotide motif, but only 50-fold in mutL- cells. The [G/C]7 sequence was destabilized the greatest and the tetranucleotide motif the least by loss of mismatch repair. These results demonstrate that the quantitative risk of mutation at various microsatellites greatly depends on the DNA sequence composition. We suggest alternative models for the production of expansion mutations during lagging strand replication of the [TTCC/AAGG]9 microsatellite.

Original languageEnglish (US)
Pages (from-to)2831-2838
Number of pages8
JournalNucleic acids research
Volume28
Issue number14
StatePublished - Jul 15 2000

Fingerprint

Mutagenesis
Microsatellite Repeats
Escherichia coli
Thymidine Kinase
Simplexvirus
Mutation
DNA Mismatch Repair
Sequence Deletion
Mutation Rate
2-acetamido-3-O-(3-acetamido-3,6-dideoxy-beta-glucopyranosyl)-2-deoxy-galactopyranose
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

@article{088c2ba4b754417ebf07b86bac8975e2,
title = "Mutational analyses of dinucleotide and tetranucleotide microsatellites in Escherichia coli: Influence of sequence on expansion mutagenesis",
abstract = "Mutagenesis at [GT/CA]10 [TC/AG]11 and [TTCC/AAGG]9 microsatellite sequences inserted in the herpes simplex virus thymidine kinase (HSV-tk) gene was analyzed in isogenic mut(L)+ and mut(L)- Escherichia coli. In both strains, significantly more expansion than deletion mutations were observed at the [TTCC/AAGG]9 motif relative to either dinucleotide motif. As the HSV-tk coding sequence contains an endogenous [G/C]7 mononucleotide repeat and ~1000 bp of unique sequence, we were able to compare mutagenesis among various sequence motifs. We observed that the relative risk of mutation in E.coli is: [TTCC/AAGG]9 > [TTCC/AAGG]10 ~ [TC/AG]11 > unique ~ [G/C]7. The mutation frequency varied 1400- fold fold in mutL+ cells between the tetranucleotide motif and the mononucleotide motif, but only 50-fold in mutL- cells. The [G/C]7 sequence was destabilized the greatest and the tetranucleotide motif the least by loss of mismatch repair. These results demonstrate that the quantitative risk of mutation at various microsatellites greatly depends on the DNA sequence composition. We suggest alternative models for the production of expansion mutations during lagging strand replication of the [TTCC/AAGG]9 microsatellite.",
author = "Kristin Eckert and G. Yan",
year = "2000",
month = "7",
day = "15",
language = "English (US)",
volume = "28",
pages = "2831--2838",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "14",

}

TY - JOUR

T1 - Mutational analyses of dinucleotide and tetranucleotide microsatellites in Escherichia coli

T2 - Influence of sequence on expansion mutagenesis

AU - Eckert, Kristin

AU - Yan, G.

PY - 2000/7/15

Y1 - 2000/7/15

N2 - Mutagenesis at [GT/CA]10 [TC/AG]11 and [TTCC/AAGG]9 microsatellite sequences inserted in the herpes simplex virus thymidine kinase (HSV-tk) gene was analyzed in isogenic mut(L)+ and mut(L)- Escherichia coli. In both strains, significantly more expansion than deletion mutations were observed at the [TTCC/AAGG]9 motif relative to either dinucleotide motif. As the HSV-tk coding sequence contains an endogenous [G/C]7 mononucleotide repeat and ~1000 bp of unique sequence, we were able to compare mutagenesis among various sequence motifs. We observed that the relative risk of mutation in E.coli is: [TTCC/AAGG]9 > [TTCC/AAGG]10 ~ [TC/AG]11 > unique ~ [G/C]7. The mutation frequency varied 1400- fold fold in mutL+ cells between the tetranucleotide motif and the mononucleotide motif, but only 50-fold in mutL- cells. The [G/C]7 sequence was destabilized the greatest and the tetranucleotide motif the least by loss of mismatch repair. These results demonstrate that the quantitative risk of mutation at various microsatellites greatly depends on the DNA sequence composition. We suggest alternative models for the production of expansion mutations during lagging strand replication of the [TTCC/AAGG]9 microsatellite.

AB - Mutagenesis at [GT/CA]10 [TC/AG]11 and [TTCC/AAGG]9 microsatellite sequences inserted in the herpes simplex virus thymidine kinase (HSV-tk) gene was analyzed in isogenic mut(L)+ and mut(L)- Escherichia coli. In both strains, significantly more expansion than deletion mutations were observed at the [TTCC/AAGG]9 motif relative to either dinucleotide motif. As the HSV-tk coding sequence contains an endogenous [G/C]7 mononucleotide repeat and ~1000 bp of unique sequence, we were able to compare mutagenesis among various sequence motifs. We observed that the relative risk of mutation in E.coli is: [TTCC/AAGG]9 > [TTCC/AAGG]10 ~ [TC/AG]11 > unique ~ [G/C]7. The mutation frequency varied 1400- fold fold in mutL+ cells between the tetranucleotide motif and the mononucleotide motif, but only 50-fold in mutL- cells. The [G/C]7 sequence was destabilized the greatest and the tetranucleotide motif the least by loss of mismatch repair. These results demonstrate that the quantitative risk of mutation at various microsatellites greatly depends on the DNA sequence composition. We suggest alternative models for the production of expansion mutations during lagging strand replication of the [TTCC/AAGG]9 microsatellite.

UR - http://www.scopus.com/inward/record.url?scp=0034661615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034661615&partnerID=8YFLogxK

M3 - Article

C2 - 10908342

AN - SCOPUS:0034661615

VL - 28

SP - 2831

EP - 2838

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 14

ER -