Ask A Scientist© Molecular Biology Archive

name         Bob W.
age          50s

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.

As I understand it, a chromosome is composed of a very long DNA
strand (up to a meter or two long), that is is wound back and
forth around molecules (whose name I forget) that look like
miniature hockey pucks. The entire length of the DNA molecule
ends up as a microscopic chromosome, so clearly there is a lot of
"bunching up" of the DNA.

Now, most texts show the splitting of DNA as an idealistic process
where a short length to the strand is unwinding and reforming as
a pair of helixes. That looks pretty convincing until one realizes
just how long the strand is, and how incredibly complex its folding
is inside the chromosome. Clearly, the diagrams in most texts
are grossly simplistic!

So (at long last) here is my question: how the heck can the DNA
manage to split (remembering that it is not only wound up in an
incredibly complex way, but is also twisted in a tight helix),
without becoming a completely tangled disaster? The problem
reminds me of attempting to cleanly split the strands of a
1000 meter long twisted rope, when the rope itself is bunched
tightly into a form that is only a a few meters long!
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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
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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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