Mismatch-repair enzyme complex

The mismatch repair enzyme complex acts during replication when an incorrect, bnt normal base (i.e., A, G, C, or T) is incorporated into the growing chain (Fig. 13.16). In bacteria, parental DNA strands contain methyl groups on adenine bases in specific sequences. During replication, the newly synthesized strands are not immediately methylated. Before methylation occurs, the proteins involved in mismatch repair can distinguish parental from newly synthesized strands. A region of the new, unmethylated strand, containing the mismatched base, is removed and replaced. 

Mismatched bases produced during DNA replication are those not conforming to or A=T base pairing. They are identified and corrected in the new strand by the mismatch-repair enzyme complex . The mismatched nucleotides are identified and excised, and the gap filled by DNA polymerase. Mutations in this complex result in failure to correct mismatched base pairs and cause hereditary non-polyposis colorectal cancer (HNPCC). 

The crystal structure of a very short patch repair (Vsr) endonuclease complex with DNA containing a TG mismatch shows novel interactions of intercalated aromatic side chains which recognise the mismatch site. The enzyme also distorts the DNA backbone, and many protein side chain interactions stabilise the complex. Crystallographic studies of duplexes containing the mutagenic... 

Additional activities that occur during replication include proofreading and DNA repair. Pol 8, which is part of the replication complex, has the 3 5 -exonuclease activity required for proofreading. Enzymes that catalyze repair of mismatched bases are also present (see section III.B.3 of this chapter). Consequently, eukaryotic replication occurs with high fidelity approximately one mis-pairing occurs for every 10 to 10 nucleotides incorporated into growing DNA chains. 

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