Abstract
Expression of serogroup B meningococcal capsular polysaccharide undergoes frequent phase variation involving reversible frameshift mutations within a homopolymeric repeat in the siaD gene. A high rate of phase variation is the consequence of a biochemical defect in methyl-directed mismatch repair. The mutator phenotype is associated to the absence of DNA adenine methyltransferase (Dam) activity in all pathogenic isolates and in 50% of commensal strains. Analysis of the meningococcal dam gene region revealed that in all Dam- strains a gene encoding a putative restriction endonuclease (drg) that cleaves only the methylated DNA sequence 5'-GmeATC-3' replaced the dam gene. Insertional inactivation of the dam and/or drg genes indicated that high rates of phase variation and hypermutator phenotype are caused by absence of a functional dam gene.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Bacterial Capsules / genetics
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Bacterial Capsules / immunology
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Base Sequence
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Cloning, Molecular
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DNA Repair / genetics
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DNA Restriction Enzymes / chemistry
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DNA Restriction Enzymes / genetics*
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Gene Expression Regulation, Bacterial / genetics
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Genes, Bacterial*
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Molecular Sequence Data
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Mutation
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Neisseria meningitidis / genetics*
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Neisseria meningitidis / pathogenicity
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Phenotype
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RNA, Messenger / analysis
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Restriction Mapping
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Sequence Alignment
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Serology
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Site-Specific DNA-Methyltransferase (Adenine-Specific) / chemistry
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Site-Specific DNA-Methyltransferase (Adenine-Specific) / genetics*
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Transformation, Genetic
Substances
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RNA, Messenger
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Dam methyltransferase
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Site-Specific DNA-Methyltransferase (Adenine-Specific)
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DNA Restriction Enzymes
Associated data
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GENBANK/AF091142
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GENBANK/AF091143