MoBio Mutation by Replication Errors Chapter 7

Replication errors are the main source of mutations. It has been estimated that uncorrected replication errors occur with a frequency of 10-9 - 10-11 for each nucleotide added by DNA polymerases. Since a cell division requires synthesis of 6 X 109 nucleotides, the mutation rate is about one per cell division.

A commonly observed replication error is the replication slippage, which occurs at the repetitive sequences when the new strand mispairs with the template strand. The microsatellite polymorphism is mainly caused by the replication slippage. If the mutation occurs in a coding region, it could produce abnormal proteins, leading to diseases. The Huntington's disease is a well known example.

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Figure 7-F-3.The mutation caused by replication slippage. In this figure, mispairing involves only one repeat. In fact, the slippage could cause several repeats to become unpaired. (a) Normal replication.(b) Backward slippage, resulting in the insertion mutation. (c) Forward slippage, resulting in the deletion mutation.