ABSTRACT
While the MMR pathway is best characterized genetically and biochemically in Escherichia coli (E. coli), substantial information has been generated over the last two decades on the biochemistry of human MMR (hMMR) (Kunkel and Erie 2005; Iyer et al. 2006). There are many strong similarities between hMMR and E.coli MMR, ranging from substrate specifi city to nick-directed strand specifi city and bidirectionality, underscoring the highly conserved nature of the evolution of MMR. However, hMMR is more complex (Jiricny 2006). Human MMR has two major biochemical functions: fi rst, effi cient recognition of the base-base mismatches and IDLs in the newly synthesized (daughter) DNA strand; and second, specifi c direction of other MMR components to allow excision, resynthesis and ligation in the daughter strand containing the erroneous genetic information. MMR has evolved to effi ciently correct errors of the DNA polymerases that escape their 3’-5’ proofreading activities during DNA replicative synthesis. However, unlike other base damage repair pathways, such as Base Excision Repair (BER) or Nucleotide Excision Repair (NER) (see Chapter 1), MMR is targeted specifi cally to the daughter strand that carries the damage.
