Question 1

What types of errors can occur during DNA replication?

Accepted Answer

Despite DNA polymerase proofreading, copying errors occur approximately every 1 million base pairs. One common error is nucleotide mismatch, such as pairing adenine with cytosine or thymine with guanine. These mismatches persist after initial proofreading and require additional repair mechanisms to maintain genetic accuracy.

Question 2

How do mismatch repair proteins identify which DNA strand contains the error?

Accepted Answer

The method depends on the organism. In E. coli, specific DNA sequences are methylated after replication, and mismatch repair proteins detect unmethylated sequences to identify the new strand. In eukaryotes, the newly synthesized strand is more likely to have DNA nicks, small breaks that mismatch repair proteins recognize and target for repair.

Question 3

What is the role of MutS and MutL proteins in mismatch repair?

Accepted Answer

MutS, a mismatch repair protein, identifies and binds to mispaired bases by detecting their abnormal structure. MutL then identifies which strand is the newly synthesized copy. Together, these proteins from the Mutator protein family coordinate the recognition and targeting of errors for repair while preserving the template strand.

Question 4

What enzymes are involved in removing and replacing incorrect nucleotides?

Accepted Answer

Exonuclease enzymes cut out the region containing the error and remove the incorrect nucleotides. DNA polymerase then fills in the correct nucleotides in their place. Finally, DNA ligase seals the sugar-phosphate backbone gaps, completing the mismatch repair process and restoring DNA integrity.

Question 5

How can defects in mismatch repair lead to cancer development?

Accepted Answer

The human homolog of MutS is MSH2. When MSH2 function is compromised, point mutations and frameshift mutations throughout the genome are not properly repaired. Humans carrying a single defective MSH2 copy have significantly higher likelihood of developing cancer due to accumulated unrepaired mutations.

Question 6

Why is a permissive mismatch repair system beneficial for bacterial survival?

Accepted Answer

A permissive mismatch repair system allows some mutations to escape correction, increasing genetic variation. This can lead to mutations conferring antibiotic resistance, improving bacterial survival when exposed to antibiotics. However, this contributes to the emergence of multidrug-resistant bacteria, posing serious challenges for human infectious disease treatment.

Question 7

What is the relationship between mismatch repair and genetic variation in populations?

Accepted Answer

While accurate mismatch repair prevents most errors, some mutations escape correction and contribute to genetic variation. This variation is essential for adaptation and evolution. However, in pathogens like Staphylococcus aureus, permissive repair systems enable rapid acquisition of antibiotic resistance, creating public health concerns through multidrug-resistant infections.

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