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Template Switching Mutation Explained
Template switching is a fascinating mechanism that can introduce various mutations into DNA during replication. Here’s a breakdown of the process:
1. Replication Fork Stalling:
Imagine the DNA double helix being unzipped during replication, with two replication forks moving along each strand. Sometimes, these forks encounter obstacles like protein knots or DNA damage, causing them to stall.
2. Misalignment and Dissociation:
Due to the stalled fork, the newly synthesized DNA strand (nascent strand) can become misaligned with its template strand. This misalignment can lead to the nascent strand dissociating from its original template.
3. Template Switching:
With the nascent strand untethered, it can search for and re-anneal with a different DNA molecule in the vicinity. This “new” template can be either the complementary strand of the original template or another nearby DNA segment.
4. Resumption of Synthesis:
DNA polymerase resumes synthesis using the new template, incorporating its sequence into the growing nascent strand. This can lead to several types of mutations depending on the nature of the new template:
Insertions: If the new template is longer than the original gap, extra nucleotides get incorporated.
Deletions: If the new template is shorter, part of the original sequence gets skipped.
Inversions: If the new template is the opposite strand of the original gap, the inserted sequence will be reversed.
Duplications: If the new template is a nearby repeated sequence, it can be copied multiple times.5. Fork Rejoining:
Eventually, the stalled replication fork restarts and rejoins with the completed nascent strand. This completes the template switching event, leaving behind a mutated DNA sequence.
As you can see, template switching is a complex process with the potential to introduce diverse mutations. Its role in various genetic diseases and genome evolution is an ongoing area of research.
Source: Bard
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I have got this answer by Hammad Rana on Quora.com:
DNA replication-related template switching is a process where the copying of genetic information involves temporarily changing the template (the strand used as a guide) during replication. In simpler terms, when cells make new copies of their DNA, sometimes they switch the strand they’re copying from.
Imagine you have a zipper with two sides, and you want to make an exact copy of it. In the DNA replication process, enzymes unzip the DNA double helix, just like opening the zipper. Now, to make a new zipper, you need a template. Usually, one side of the unzipped DNA acts as the template for the new copy.
But here’s where template switching comes in. Occasionally, during replication, the copying process might switch from one side to the other, like if you started copying from the left side of the zipper and then switched to the right side for a little bit. This switching can happen for various reasons, including the presence of certain DNA structures or obstacles.
In the end, you end up with a new DNA strand that has information from both sides of the original DNA, kind of like a zipper made from both the left and right sides. Template switching is a normal part of the DNA replication process and contributes to genetic diversity.
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