problem with a long multi-stranded rope:
start in the middle and try to pull the
strands apart. It will soon become too
hard to unwind because of the resistance
of the extra twists on both sides of the
separation point. If you let go, the rope
will tend to coil back upon itself—think
also of the coiled cords on older telephones which too easily become tangled
into coils upon coils. To compensate for
every added twist in the forward direction, the DNA behind the unwinding site
adds a twist, and also becomes super-coiled (overwound). In a cell, if the DNA
were prevented from unwinding, then
the cell could no longer make proteins
or copy itself.
Detangling machines
The Creator solved this problem in living
creatures with special protein machines
(enzymes) called topoisomerases. 3 They
cut the DNA, rearrange it, and stick it
back together. They must work ahead
of the replication fork to keep the DNA
from over-winding.
There are several classes of topoiso-
merases, but they are grouped into two
main types:
• Type 1 topoisomerase cuts one of
the DNA strands and temporarily
bonds to both ends of the cut. Then
the uncut strand is free to pass
through the break. In either case,
this relieves or ‘relaxes’ the strain,
one twist at a time. Finally, the break
is reconnected; this is called ligation.
Type 1 topoisomerases don’t
need ATP—the energy built up by
the DNA’s over-winding is simply
released, like a coiled spring when
let go.
• Type II topoisomerases are more
complex. This type cuts both
strands of the double helix and
holds them apart. It then pulls a
loop of the double helix from a
non-cut section through the break.
After that, the two strands are
reconnected, the passed-through
DNA is released, and finally the
enzyme releases the reconnected
DNA so the process can be repeated
as necessary. This requires
ATP for several of these steps.
Type II topoisomerase is impor-
tant for another reason: when DNA
is replicated, sometimes the two
‘daughter’ DNA molecules can end
up wound around each other like
links in a chain, i.e. catenated (Latin
catena = chain). Thus, separating
these linked molecules is called
decatenation, and this is a vital role
of the type II topoisomerase.
Useless unless fully functional
These enzymes must do three things,
otherwise they would be useless or
even harmful: cut, move another strand
through the cut, and reconnect. To show
how important each step is, if any one
step is disabled, the enzyme doesn’t
work and the cell dies.
Indeed, some antibacterial and anti-cancer drugs work by targeting topoisomerases. The class of antibiotics called
fluoroquinolones (e.g. ciprofloxacin,
levofloxacin) stops the reconnecting
step of bacterial type II topoisomerase,
leading to increasing breaks in the DNA,
DNA replication or DNA synthesis is the process of copying a double-stranded DNA molecule. This process is paramount to
all life as we know it. Disclaimer: This is a simple diagram of very intricate pieces of machinery (e.g. helicase has a ring
structure that the DNA strand passes through).
