A molecular biologist has discovered a new strain of bacteria that utilizes a sequence other than GATC to guide its mismatch repair activities. Which of the following sequences cannot be used by this new bacterium for mismatch repair?
The correct answer and explanation is :
The correct answer is: Any palindromic sequence that lacks distinguishable methylation or modification patterns.
A palindromic sequence is a DNA sequence that reads the same forward and backward on complementary strands. Mismatch repair (MMR) relies on distinguishing between the old (parental) and new (nascent) DNA strands, typically using methylation as a marker in bacteria like Escherichia coli. E. coli uses GATC sequences, where the parental strand is methylated at the adenine by Dam methylase. The newly synthesized strand remains temporarily unmethylated, allowing mismatch repair proteins (MutH, MutL, and MutS) to identify and correct errors.
For a newly discovered bacterial strain using a different sequence for MMR, the chosen sequence must have two key features:
- It must be methylated or modified on the parental strand to enable strand discrimination.
- It should not be fully palindromic without distinguishable modifications, as fully palindromic sequences (e.g., GAATTC of EcoRI) could be methylated identically on both strands, preventing discrimination between old and new DNA.
Thus, sequences that lack an asymmetric methylation pattern or modifications that allow strand distinction cannot be used for mismatch repair. A fully symmetric sequence like CCGG (recognized by MspI and HpaII restriction enzymes) is a poor choice because it is methylated identically on both strands, making it impossible to determine which strand is the parental one.
Conclusion:
The newly discovered bacteria must use a sequence that enables strand discrimination, such as a non-palindromic or hemi-methylated sequence. If a fully symmetric sequence is used without additional modifications, mismatch repair would fail, leading to uncorrected DNA replication errors.