Methyl directed DNA mismatch repair in Vibrio cholerae.
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Date
1994-12
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Abstract
Mismatches in DNA occur either due to replication error or during recombination
between homologous but non-identical DNA sequences or due to chemical modification of
bases. The mismatch in DNA, if not repaired, result in high spontaneous mutation frequency.
The repair has to be in the newly synthesized strand of the DNA molecule, otherwise the
error will be fixed permanently. Three distinct mechanisms have been proposed for the
repair of mismatches in DNA in prokaryotic cells and gene functions involved in these
repair processes have been identified. The methyl-directed DNA mismatch repair has been
examined in Vibrio cholerae, a highly pathogenic gram negative bacterium and the causative
agent of the diarrhoeal disease cholera. The DNA adenine methyltransferase encoding gene
(dam) of this organism which is involved in strand discrimination during the repair process
has been cloned and the complete nucleotide sequence has been determined. Vibrio cholerae
dam gene codes for a 21ยท5 kDa protein and can substitute for the Escherichia coli enzyme.
Overproduction of Vibrio cholerae Dam protein is neither hypermutable nor lethal both in
Escherichia coli and Vibrio cholerae. While Escherichia coli dam mutants are sensitive to
2-aminopurine, Vibrio cholerae 2-aminopurine sensitive mutants have been isolated with
intact GATC methylation activity. The mutator genes mutS and mutL involved in the
recognition of mismatch have been cloned, nucleotide sequence determined and their products
characterized. Mutants of mutS and mutL of Vibrio cholerae have been isolated and show
high rate of spontaneous mutation frequency. The mutU gene of Vibrio cholerae, the product
of which is a DNA helicase II, codes for a 70 kDa protein. The deduced amino acid
sequence of the mutU gene hs all the consensus helicase motifs. The DNA cytosine
methyltransferase encoding gene (dam) of Vibrio cholerae has also been cloned. The dcm
gene codes for a 53 kDa protein. This gene product might be involved in very short patch
(VSP) repair of DNA mismatches. The vsr gene which is directly involved in VSP repair
process codes for a 23 kDa protein. Using these information, the status of DNA mismatch
repair in Vibrio cholerae will be discussed.
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Keywords
Spontaneous mutation frequency, mutator genes, strand discrimination, methylation, nucleotide sequence, very short patch repair
Citation
Bandyopadhyay Rupa, Sengupta Aditya, Bera Tapan K, Bhakat Kishor K, Dutta Chitra, Das Jyotirmoy. Methyl directed DNA mismatch repair in Vibrio cholerae. Journal of Biosciences. 1994 Dec; 19(5): 557-564.