title: Chromosomal directionality of DNA mismatch repair in Escherichia coli.
abstract: Defects in DNA mismatch repair (MMR) result in elevated mutagenesis and in cancer predisposition. This disease burden arises because MMR is required to correct errors made in the copying of DNA. MMR is bidirectional at the level of DNA strand polarity as it operates equally well in the 5' to 3' and the 3' to 5' directions. However, the directionality of MMR with respect to the chromosome, which comprises parental DNA strands of opposite polarity, has been unknown. Here, we show that MMR in Escherichia coli is unidirectional with respect to the chromosome. Our data demonstrate that, following the recognition of a 3-bp insertion-deletion loop mismatch, the MMR machinery searches for the first hemimethylated GATC site located on its origin-distal side, toward the replication fork, and that resection then proceeds back toward the mismatch and away from the replication fork. This study provides support for a tight coupling between MMR and DNA replication.
authors.affiliation: Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF United Kingdom.
authors.forename: A M Mahedi
authors.initials: AM
authors.lastname: Hasan
authors.affiliation: Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF United Kingdom D.Leach@ed.ac.uk.
authors.forename: David R F
authors.initials: DR
authors.lastname: Leach
mesh_terms: D020137:Base Pair Mismatch; D001665:Binding Sites; D001761:Bleomycin / Q000737:chemistry; D002876:Chromosomes, Bacterial / Q000648:ultrastructure*; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D004261:DNA Replication; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics; D009154:Mutation; D009711:Nucleotides / Q000235:genetics; D010641:Phenotype; D053484:RecQ Helicases / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: D029968:Escherichia coli Proteins; D009711:Nucleotides; D001761:Bleomycin; C105427:Zeocin; D051719:MutS DNA Mismatch-Binding Protein; D053484:RecQ Helicases
keywords: E. coli; mismatch repair; recombination