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Name: Bob W.
Status: Other
Age: 50s
Location: N/A
Country: N/A
Date: N/A 


Question:
Hi, I have a "mechanical" question about DNA replication during cell division.

I understand the basic way that chromosomes replicate, where the DNA strand splits in two and free base pairs form on each strand- half to result in two identical strands of DNA. However it seems to me (as a mechanical engineer), that there are some basic "mechanical" problems with this.



Replies:
Hi Bob, as a 50 something high school biology teacher, I think I can help you understand some of these mechanics. Yes, you are right when you say the diagrams have got to be too simplistic. They are teaching the overall concept and not the precise procedure. DNA replication is a family of chemical reactions which involves many steps that take place simultaneously up and down the DNA strand at lightening speeds. One of the most important points is that DNA is unwound in thousands of places along its length at the same moment by the action of various enzymes. In as many places as these molecules are in action, so too, are the helicase enzymes which break the weak hydrogen bonds holding the strands together. Now there are thousands of replications forks from one end of the strand to the other.

Think about pulling apart the strands of twisted twine in lots of places so it looks like there are lots of loops formed. DNA replication begins even as the replication forks are forming so that as a double stranded molecule is pulling apart to become a single stranded molecule it is at the same time also developing double strandedness again along the single edges that are not even completely freed from one another! This process of plugging in the proper nucleotides is overseen by a family of polymerase enzymes which also check to see if the right base has been put in. These gluing and proof reading enzymes make a gluing/proofing goof about once in ten to the negative ninth times. Hence there are occassional mutations in the replication process.

Almost at the same time the polymerases are at work, along comes another family of enzymes which re-wrap the helx and re-curl the strand around the associated nucleosomes (your hockey pucks). This is an incredibly complex, biochemical reaction which takes place under the influences of molecular distances, electromagnetic charges, conformational changes in molecules, concentration gradients of enzymes and substrates, and critical pH and thermodynamic energy levels. To truly understand the replication process, beyond what you see in most introductory textbooks, you need to have a firm foundation in advanced biochemical topics. The question I always find fascinating, though, is not in regard to the mechanics but rather in regard to the origin of this process.

You see, all enzymes are proteins; protein synthesis must be directed by DNA; however, DNA replication cannot take place without these proteins. Sooooo, what came first? The protein or the DNA? I recommend Mark Ridley's best-seller The Human Genome for more enlightenment.

Cherie Breffeilh


Very insightful. There are numerous enzymes involved in the process that each have a job to do. Some of these enzymes are responsible for opening the helix and stabilizing it as it replicates. Also, replication occurs at numerous places along the chromosome at the same time. So there are numerous copies of each kind of enzyme working together to get the job done. Also, another complication is that the two strands are not replicated in the same way. One of the strands is replicated in one sweep, but the other strand is replicated in short fragments which in the end are "stitched" together.

When one considers the E. coli bacterium, that has a life cycle of 20 minutes, and the fact that this process must occur and be done faithfully every 20 minutes, it is a wonder.

vanhoeck



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