Practice question

Eukaryotic mismatch repair retains conserved MutS homologs MSH2/MSH6 for mismatch recognition and MutL homologs MLH1/PMS2 for coordination, but lacks MutH ortholog entirely. Strand discrimination does not depend on Dam methylation, absent in eukaryotes. Instead, naturally occurring nicks associated with lagging strand Okazaki fragment termini, leading strand replication discontinuities, or PCNA-bound MutL endonuclease activity create entry points for EXO1 exonuclease. MutLα itself displays latent endonuclease regulated by PCNA and ATP. Therefore, eukaryotic system achieves directionality without methylation-directed MutH cleavage, representing mechanistic divergence.