Very short patch repair: reducing the cost of cytosine methylation.
In Escherichia coli and related bacteria, the product of gene dcm methylates the second cytosine of 5'-CCWGG sequences (where W is A or T). Deamination of 5-methylcytosine (5meC) results in C to T mutations. The mutagenic potential of 5meC is reduced by a system called very short patch (VSP) repair, which replaces T with C. T:G and U:G mispairs in the methylatable sequence and in related sequences are recognized by the product of vsr, a gene adjacent to dcm. Vsr creates a nick just 5' of the mispaired pyrimidine to initiate the repair. Additional products known to be required for VSP repair are DNA polymerase I and DNA ligase. MutS and MutL have a stimulatory role but are not required. The ability of Vsr to recognize T:G mispairs in sequences related to CCWGG is probably responsible for over- and under-representation of certain tetranucleotides in the E. coli genome. Although VSP repair reduces spontaneous mutations at 5meCs in replicating bacteria, mutation hot-spots persist at these sites. Under conditions that more accurately mimic the natural environment of E. coli, VSP repair appears to be effective in preventing mutation at 5meC.
Lieb
M
M
Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Bhagwat
A S
AS
D000595:Amino Acid Sequence; D001483:Base Sequence; D003596:Cytosine; D004260:DNA Repair; D004269:DNA, Bacterial; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016680:Genome, Bacterial; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides
D004269:DNA, Bacterial; D009841:Oligonucleotides; D003596:Cytosine; D004706:Endodeoxyribonucleases; C071421:vsr endonuclease