My husband and I are hopelessly addicted to the TV show
Fringe. We’re consistently a season
behind because we choose to watch once the episodes are out on DVD. While I can hardly sit still to watch a two
hour movie, I’ll happily stay up late watching more and more episodes of a good
TV show (this
also includes - but is not limited to - Game of Thrones, Rome, Mad Men, Prison
Break, Lost, Big Love, Nip/Tuck, and The Tudors. We’re looking forward to Boardwalk Empire,
Downton Abbey, and Breaking Bad, as well).
Most recently, the Fringe shape-shifters
were attacking humans in our universe. A
shape-shifter is a specialized being who can take on the look of someone else;
the same idea is found in Harry Potter’s Polyjuice Potion or X-Men’s Rebecca
Romijn. However, these Fringe suckers
are extra cool because not only can they look like someone else, but their
cells will actually have the DNA of the person.
Unfortunately for the shape-shifters, the transformations aren’t
happening correctly. In an effort to
figure out their problems so their pursuit of world-domination can continue, a
rather meek looking shape-shifter named Nadine captured a biochemist under the
guise of asking for help to cure her shape-shifter-ness. Once this biochemist catches on to the fact that
Nadine is up to no good, he tries to add restriction enzymes to a serum he
intends to give her. She grabs his hand
saying “I know a thing about biochemistry and enzymology! Those restriction enzymes will destroy my DNA
and, thus, me.”
I
raised my eyebrows at this statement, then chuckled, then furrowed my brow
trying to decide if this far-fetched idea would indeed kill the mythical
shape-shifter (because, yes, ALL of this can
happen, folks).
But,
let’s back it up here. What in the world
is a restriction enzyme in the first place?
I’ve
talked about enzymes before – they are specialized proteins designed to perform
one specific reaction. In the Fun with Radioactivity post, I discussed how one class of enzymes called kinases
will move a phosphate group from one protein to another. Restriction enzymes are a different class of
enzymes and they cut DNA at very specific places.
One of the
first restriction enzymes discovered came from the bacteria Haemophilus influenzae. Scientists originally believed this was the
cause of influenza, hence its name. In
1968, several biochemists at Johns Hopkins University isolated an enzyme from H. influenzae and named it HindIII.
HindIII = Haemophilus influenza, strain d, third
enzyme isolated
This
enzyme will cleave DNA whenever it comes across this exact sequence: A A G C T
T. Wherever it sees this EXACT string of DNA bases, HindIII will bind to that area and cut
the DNA in half. Disrupting a DNA
molecule in this way will destroy its usefulness. Think about burning a hole in the middle of a
recipe card, then another hole somewhere else, and so on... – you’re slowly destroying the card and all the information written
on it (Central Dogma post). Genomes (entire DNA
molecules) are very large! You can
imagine that the enzyme will run into A A G C T T quite often simply by the
rules of chance. HindIII never misses an opportunity – it will find it and it will
cut the DNA.
As time
went on, more and more of these types of enzymes were isolated from different
bacteria. I believe the current number
is somewhere in the hundreds (a list of restriction enzymes and the sequences they cut can
be found here: LINK). Each one of
the restriction enzymes listed recognizes a very specific stretch of DNA bases
and will cut the DNA when it finds with that sequence. Every time.
Without fail.
At this
point, you might be scratching your head.
If bacteria have so many of these enzymes that are responsible for
cutting and destroying DNA, then how are the bacteria alive? Wouldn’t these enzymes chew up the bacteria’s
own DNA and kill it?
Ah. That’s where the word “restriction” comes
into play!
Scientists
believe that bacteria developed these enzymes as a defense mechanism. I’ve talked about how cells can be invaded (Influenza, HPV,
amoebas, infections of the kidney!) and bacteria are no different. They can also be invaded. Viruses that specifically infect bacteria are
called phage. Unsurprisingly, phage carry their own genomes
and are ready to hijack the bacteria to do its bidding. But!
The bacteria have these restriction enzymes to restrict what can come inside. These enzymes will chew up the phage’s DNA
and not theirs as long as the enzymes can tell the difference. Typically, bacteria will decorate their own
DNA with a chemical group called a methyl group. Restriction enzymes are unable to bind to
methylated DNA. Unfortunately for phage,
their DNA isn’t methylated and thus vulnerable to the restriction enzymes.
Rather
smart, aren’t the bacteria? Bacteria are
actually fascinatingly interesting. They
are far simpler than a human being but sophisticated in so many ways. Scientists have learned an immeasurable amout
of knowledge concerning life and its mysteries by studying bacteria.
So, now
we know what a restriction enzyme is and what it does, but we haven’t answered
the most burning question of all: can they kill a shape-shifter?
Well –
probably not.
The biochemist on Fringe put a mixture of
restriction enzymes into a serum he planned to inject into Nadine.
Let’s say he was successful at
injecting the serum. Now, the enzymes
are floating around in her bloodstream.
Their nearest available cells are going to be red blood cells, which
carry no genome and would be unaffected by restriction enzymes, and white blood
cells. In order to destroy the white
blood cells (or ANY cell), the
restriction enzymes must be able to get across the cell membrane. That’s easy if you are small, like water, but
much much MUCH more difficult if you
are a large protein. It’s like trying to
fit an elephant through your white picket fence. You need a door or a hole, which aren’t
readily available.
Let’s say they could get in,
though. Genomes are precious and
therefore protected in the nucleus, which is another fence to force their way
through.
But okay, let’s say they get across
the plasma membrane and the nuclear membrane, now what does it face? Our genomes are very packaged (unlike phage and
bacterial genomes). All the individual
bases aren’t readily accessible so the enzymes might be able to cut here and there,
but certainly they wouldn’t destroy the whole molecule. It’s far too protected.
Our bodies also have another
defense in their midst – immune response.
Like restriction enzymes, our bodies know what belongs inside us and
what does not. Most certainly a strange
new enzyme would be detected by our immune system and attacked. The immune response isn’t always perfect - we
do get sick, of course - but our bodies “fight off infection” in a reasonable
time period.
100% of Fringe is far-fetched, but
c’mon! They’re so creative with the
available scientific knowledge. I
appreciate it!
Phage: Also called “bacteriophage,”
these are viruses that infect bacteria
Methyl group: One carbon
atom bound to three hydrogen atoms. These groups are placed on DNA as a way to
mark it.
NOTE: The scientists credited with the discovery of restriction enzymes, Werner Arber, Daniel Nathans, and Hamilton O. Smith, were awarded the 1978 Nobel Prize in Physiology or Medicine. Restriction enzymes are used every single day in labs all over the world to cut DNA. I could list off about fifty different enzymes I've used in my entire ten years working in the lab. They are essential to Step 1 of purifying a protein, as discussed in From DNA to Protein, Step 1.
REFERENCES
History of Restriction Enzymes: http://www.nature.com/scitable/topicpage/restriction-enzymes-545
Alberts et al. "Molecular Biology of the Cell, 4th Edition." Garland Science, New York, New York (2002).
Smith and Wilcox. "A restriction enzyme from Hemophilus influenzae. I. Purification and general properties." (1970) J Mol. Biol. 51(2) pgs 379 - 391
Nobel Prize Winners of 1978: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1978/
