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PMID: 10908342 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Nucleic acids research ·Vol. 28 ·No. 14 ·2000-07-15 ·Pages 2831-8

Eckert KA, Yan G

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 mutL(+) and mutL(-) 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 approximately 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) > [GT/CA](10) approximately [TC/AG](11) > unique approximately [G/C](7). The mutation frequency varied 1400-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.

MeSH Terms
Adenosine Triphosphatases Bacterial Proteins/genetics,physiology Base Pair Mismatch DNA Repair DNA, Recombinant/genetics Dinucleotide Repeats/genetics Escherichia coli/genetics Escherichia coli Proteins Microsatellite Repeats/genetics MutL Proteins Mutation Plasmids Simplexvirus/enzymology Thymidine Kinase/genetics
Chemicals
Bacterial Proteins DNA, Recombinant Escherichia coli Proteins MutL protein, E coli Thymidine Kinase Adenosine Triphosphatases MutL Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Eckert K A
The Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA. kae4@psu.edu
Yan G
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/28.14.2831
Email
kae4@psu.edu
Published
2000-07-15
Pages
2831-8
Language
English
Region
England
NLM ID
0411011
PMCID
PMC102660
Subset
IM
Grants
NCI NIH HHS · CA73649 · United States
External Links
PubMed source DOI: 10.1093/nar/28.14.2831 PMC Full Text View journal details
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