When the roof leaked and the grain molded, mice appeared. Jan Baptista van Helmont, a seventeenth century Flemish scientist, proposed that mice could arise from rags and wheat kernels left in an open container for 3 weeks. 

TLS Online TPP Program

#Id: 6113

#Unit 3. Fundamental Processes

In Escherichia coli, MutS scans the DNA, recognizing mismatches from the distortion they cause in the DNA backbone. 

MutS has an ATPase activity that is required for mismatch repair and recruits MutL, a second protein component of the repair system. MutL, in turn, activates MutH, an enzyme that causes an incision or nick on one strand near the site of the mismatch. Nicking is followed by the action of a specific helicase (UvrD) helicase unwinds the DNA, starting from the incision and moving in the direction of the site of the mismatch, and the filled in by DNA polymerase III

TLS Online TPP Program

#Id: 6114

#Unit 3. Fundamental Processes

MutH protein binds at hemimethylated daughter strands created by dam methylase

TLS Online TPP Program

#Id: 6115

#Unit 3. Fundamental Processes

TLS Online TPP Program

#Id: 6116

#Unit 3. Fundamental Processes

The main MutS homologs in most eukaryotes are MSH2 (MutS homolog), MSH3, and MSH6.

TLS Online TPP Program

#Id: 6117

#Unit 3. Fundamental Processes

Longer mismatches (2 to 6 bp) recognized by heterodimer of MSH2 and MSH3.  Homologs of MutL, predominantly a heterodimer of MLH1 (MutL homolog) and PMS1 (post-meiotic segregation), bind to and stabilize the MSH complexes

TLS Online TPP Program

#Id: 6118

#Unit 3. Fundamental Processes

The hMutb complex, a Msh2-Msh3 dimer, binds mismatched insertion/deletion/slippage loops, while the Msh2-Msh6 (hMuta) complex binds to single-base mismatches.