PMID- 10230396 OWN - NLM STAT- MEDLINE DCOM- 19990527 LR - 20190915 IS - 1097-2765 (Print) IS - 1097-2765 (Linking) VI - 3 IP - 4 DP - 1999 Apr TI - Hypermutation in pathogenic bacteria: frequent phase variation in meningococci is a phenotypic trait of a specialized mutator biotype. PG - 435-45 AB - 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. FAU - Bucci, C AU - Bucci C AD - Dipartimento di Biologia e Patologia, Cellulare e Molecolare, L. Califano, Universita di Napoli Federico II, Centro di Endocrinologia ed Oncologia Sperimentale G. Salvatore of the Consiglio Nazionale delle Ricerche, Italy. FAU - Lavitola, A AU - Lavitola A FAU - Salvatore, P AU - Salvatore P FAU - Del Giudice, L AU - Del Giudice L FAU - Massardo, D R AU - Massardo DR FAU - Bruni, C B AU - Bruni CB FAU - Alifano, P AU - Alifano P LA - eng SI - GENBANK/AF091142 SI - GENBANK/AF091143 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (RNA, Messenger) RN - EC 2.1.1.72 (Dam methyltransferase) RN - EC 2.1.1.72 (Site-Specific DNA-Methyltransferase (Adenine-Specific)) RN - EC 3.1.21.- (DNA Restriction Enzymes) SB - IM MH - Amino Acid Sequence MH - Bacterial Capsules/genetics/immunology MH - Base Sequence MH - Cloning, Molecular MH - DNA Repair/genetics MH - DNA Restriction Enzymes/chemistry/*genetics MH - Gene Expression Regulation, Bacterial/genetics MH - *Genes, Bacterial MH - Molecular Sequence Data MH - Mutation MH - Neisseria meningitidis/*genetics/pathogenicity MH - Phenotype MH - RNA, Messenger/analysis MH - Restriction Mapping MH - Sequence Alignment MH - Serology MH - Site-Specific DNA-Methyltransferase (Adenine-Specific)/chemistry/*genetics MH - Transformation, Genetic EDAT- 1999/05/07 00:00 MHDA- 1999/05/07 00:01 CRDT- 1999/05/07 00:00 PHST- 1999/05/07 00:00 [pubmed] PHST- 1999/05/07 00:01 [medline] PHST- 1999/05/07 00:00 [entrez] AID - S1097-2765(00)80471-2 [pii] AID - 10.1016/s1097-2765(00)80471-2 [doi] PST - ppublish SO - Mol Cell. 1999 Apr;3(4):435-45. doi: 10.1016/s1097-2765(00)80471-2.