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MISMATCH REPAIR, MMR

Repair of mismatches is performed by a set of specific proteins:

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/Mismatch-repair.jpg

Two kinds of mismatch are recognised:

  • Mispairing, which occurs normally at very low frequency, increased when e.g. 8-oxoguanine is present in replicating DNA:
http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/mispairing.jpg

  • Slippage occurring during replication of DNA containing repetitive sequences:
http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/slippage.jpg

START ANIMATION

If slippage occurs in the template strand, as here, the daughter strand has a deletion. It can also occur in the daughter strand, leading to insertion of sequence.

The human disease HNPCC (hereditary non-polyposis colon cancer) is associated with microsatellite instability (sequence variability in sections of DNA with di- or tri-nucleotide repeats.
Microsatellite instability is a feature of bacteria with a defect in mismatch repair.
Homologues of MMR genes are defective in HNPCC: hMSH2, hMLH1, hPMS2.
Expression of the MMR defect depends on loss of the normal allele in the tumour.
MMR inactivation gives rise to a mutator phenotype.

More on DNA repair