How does DNA polymerase attempt to correct mismatches during DNA replication?

DNA polymerase is the enzyme that makes a new DNA strand by reading the existing strand as a template. It adds nucleotides one by one to form a complementary strand. But sometimes, it inserts the wrong nucleotide that does not correctly match the template base. This causes a mismatch in the DNA sequence, which can lead to mutations if not fixed.

To prevent such errors, DNA polymerase has a special ability called proofreading, which acts as the first line of defense during replication. This proofreading helps detect and correct mismatches immediately. The process happens in several steps:

1. Mismatch Detection

As the polymerase adds each nucleotide, it checks whether the newly added base forms a proper base pair with the template base. The correct base pairing forms a regular and stable structure, but a mismatch creates a bulge or irregular shape. This structural distortion is immediately detected by DNA polymerase.

2. Pause in Replication

Once the mismatch is recognized, the enzyme stops further addition of nucleotides. This pause is important as it allows DNA polymerase to shift from its synthesis mode to its correction mode. Without this pause, the enzyme might continue adding wrong bases, making the problem worse.

3. Removal of Incorrect Base

DNA polymerase has an additional enzymatic function called 3' to 5' exonuclease activity. Using this function, the enzyme moves backward along the newly made strand and removes the incorrect nucleotide from the 3' end. This removal is very specific and targets only the last base added.

4. Addition of Correct Base

After removing the wrong base, DNA polymerase repositions itself and chooses the correct nucleotide. It uses the template strand again to determine which base should be added. The correct base is then added at the same position where the error was made.

5. Resuming DNA Synthesis

Once the correction is completed, DNA polymerase resumes its regular 5' to 3' polymerising activity and continues replication. The strand continues to grow with the correct sequence of nucleotides.







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