Chromosomal directionality of DNA mismatch repair in Escherichia coli

A M Mahedi Hasan, David R F Leach

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)9388-93
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Volume112
Issue number30
Early online date13 Jul 2015
DOIs
Publication statusPublished - 28 Jul 2015

Keywords / Materials (for Non-textual outputs)

  • E. coli
  • mismatch repair
  • recombination

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