title: Mutations in polI but not mutSLH destabilize Haemophilus influenzae tetranucleotide repeats.
abstract: Haemophilus influenzae (Hi), an obligate upper respiratory tract commensal/pathogen, uses phase variation (PV) to adapt to host environment changes. Switching occurs by slippage of nucleotide repeats (microsatellites) within genes coding for virulence molecules. Most such microsatellites in Hi are tetranucleotide repeats, but an exception is the dinucleotide repeats in the pilin locus. To investigate the effects on PV rates of mutations in genes for mismatch repair (MMR), insertion/deletion mutations of mutS, mutL, mutH, dam, polI, uvrD, mfd and recA were constructed in Hi strain Rd. Only inactivation of polI destabilized tetranucleotide (5'AGTC) repeat tracts of chromosomally located reporter constructs, whereas inactivation of mutS, but not polI, destabilized dinucleotide (5'AT) repeats. Deletions of repeats were predominant in polI mutants, which we propose are due to end-joining occurring without DNA polymerization during polI-deficient Okazaki fragment processing. The high prevalence of tetranucleotides mediating PV is an exceptional feature of the Hi genome. The refractoriness to MMR of hypermutation in Hi tetranucleotides facilitates adaptive switching without the deleterious increase in global mutation rates that accompanies a mutator genotype.
authors.affiliation: Molecular Infectious Diseases Group, Department of Paediatrics, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. cbayliss@molbiol.ox.ac.uk
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Bayliss
authors.forename: Tamsin
authors.initials: T
authors.lastname: van de Ven
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
mesh_terms: D000251:Adenosine Triphosphatases; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D020137:Base Pair Mismatch; D004256:DNA Polymerase I / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018900:Dinucleotide Repeats; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D029968:Escherichia coli Proteins; D006193:Haemophilus influenzae / Q000201:enzymology* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D018895:Microsatellite Repeats; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; D016296:Mutagenesis
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D018985:Epitopes, B-Lymphocyte; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; C074770:MutL protein, E coli; D004256:DNA Polymerase I; D004706:Endodeoxyribonucleases; C059682:methyl-directed mismatch repair protein, E coli; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli; D045643:DNA Repair Enzymes