An individual inherits two defective copies of the MLH1 gene, a protein involved

Question

An individual inherits two defective copies of the MLH1 gene, a protein involved in mismatch repair of DNA during its replication. What do you predict will be the consequences of deficient mismatch repair upon DNA replication?

a. The fidelity of DNA polymerase activity will be decreased.

b. Mismatched nucleotides will no longer be detected by the replication complex.

c. Ligase will not be able to repair nicks in the DNA.

d. There will be a higher frequency of nucleotides damaged by external agents.

e. A higher frequency of mutations will become fixed in the newly synthesized strand.

Explanation / Answer

e. A higher frequency of mutations will become fixed in the newly synthesized strand.

DNA mismatches arise when one base is improperly paired with another base, or when there is an insertion or deletion of a short segment in one strand of DNA that is not matched to the DNA sequences of the other complementary strand.

MLH1 protein is one component of a system of seven DNA mismatch repair (MMR) proteins. All these proteins work coordinately in sequential steps for initiating DNA mismatch repairs. A deficient mismatch repair upon DNA replication results in microsatellite instability (MSI) and a higher frequency of spontaneous mutations. About 13% of colorectal cancers are caused due to a deficient mismatch repair.

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