Question 1

What are mismatched base pairs and how do they occur during DNA replication?

Accepted Answer

Mismatched base pairs, such as adenine paired with cytosine instead of thymine, occur when errors escape the proofreading ability of DNA polymerase during replication. Despite proofreading mechanisms, approximately one copying error occurs per million base pairs replicated. These mismatches include incorrect pairings like A with G or T with C, which must be detected and corrected by cellular repair systems.

Question 2

How does the MutS protein identify mismatched bases in bacterial mismatch repair?

Accepted Answer

MutS, the mismatch recognition protein in E. coli, identifies mismatched bases by detecting their abnormal structure compared to correctly paired bases. Once MutS binds to a mismatch, it recruits MutL to form the MutS-MutL complex. This activated complex then stimulates MutH, an endonuclease enzyme, to nick the newly synthesized DNA strand at specific sites.

Question 3

Why is DNA methylation important for identifying the new strand in mismatch repair?

Accepted Answer

In E. coli, genomic DNA receives methyl groups at specific sites, but newly synthesized strands are not immediately methylated. This temporary difference in methylation status allows the repair complex to distinguish the new strand from the template strand. MutH nicks the unmethylated new strand while leaving the template strand intact, ensuring only the erroneous strand is repaired.

Question 4

What is the step-by-step process for repairing a mismatched base pair?

Accepted Answer

After MutH nicks the new strand, a helicase unwinds the DNA segment from the template. An exonuclease then hydrolyzes and removes the erroneous region, creating a gap. DNA polymerase fills this gap with correct nucleotides, and DNA ligase seals the sugar-phosphate backbone, completing the repair and restoring proper base pairing.

Question 5

How do eukaryotes identify newly synthesized DNA strands for mismatch repair?

Accepted Answer

Eukaryotes use two mechanisms to identify new strands: methylation patterns and DNA nicks. Like prokaryotes, cytosine and adenine bases in newly synthesized strands receive methyl groups after replication. Additionally, the new strand in eukaryotes is more likely to contain small breaks called DNA nicks, which repair proteins recognize and target for correction.

Question 6

What happens when mismatch repair genes are defective in humans?

Accepted Answer

Defects in human mismatch repair genes like MSH2, the homolog of bacterial MutS, allow point mutations and frameshift mutations to accumulate throughout the genome. Individuals carrying a single compromised copy of MSH2 have significantly higher cancer risk because unrepaired mutations can lead to malignant cell transformation and tumor development.

Question 7

How do mutations from imperfect mismatch repair affect bacterial populations?

Accepted Answer

A permissive mismatch repair system in bacteria can generate mutations conferring antibiotic resistance, increasing bacterial survival when exposed to antibiotics. While this genetic variation benefits bacterial populations through adaptation and reproduction, it creates serious challenges for human medicine by accelerating the spread of antibiotic-resistant pathogens.

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