Answer to Question 4 from October, 2000

4. Using no more than four sentences, describe how bacteria and mammalian cells distinguish the template strand from the nascent strand during mismatch repair. (5 points)

Bacteria methylate the A residues in the sequence GATC, but this methylation doesn't occur until several minutes after replication is complete. Thus, in newly replicated DNA (where most mismatch errors are located), the template strand is methylated while the nascent strand is not, and the MutH protein recognizes this difference.

Available evidence suggests that mammalian cells do not use methylation to distinguish nascent from template strands. Some evidence suggests that, instead, mammalian cells rely on the higher frequency of nicks (due to Okazaki fragments) in nascent DNA.

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