Julia Collins - DNA, or Knot DNA? That Is The Question

Outline An Introduction to Knot Theory Some Biology revision Knotted DNA Conclusion
DNA, or knot DNA? That is the question.

1 2
Julia Collins
1st February 2007
1
Disclaimer: This is in fact not the question.
2
Warning:This product may contain traces of nuts.
1
An Introduction to Knot Theory
2
Some Biology revision
3
Knotted DNA
4
Conclusion
The Actual Questions
How can knot theory help us to distinguish DNA molecules?
How can knot theory help biologists to understand the ways in
which enzymes act on DNA?
How can knot theory give us estimates of the rates at which
enzymes act on DNA?
enzymes act on DNA?
enzymes act on DNA?
Not a knot?
The kind of knot you tie in your shoelaces is not a
mathematical knot!
A mathematical knot is a simple (oriented) closed curve in R
3
.
A link is a collection of knots, which may or may not be linked
together.
Examples
Not a knot?
mathematical knot!
3
.
together.
Examples
Not a knot?
mathematical knot!
3
.
together.
Examples
Not a knot?
mathematical knot!
3
.
together.
Examples
How to know if youre a secret knot theorist
What every knot theorist wants most of all is to be able to tell
when two knots are the same.
Denition
We say that two knots are equivalent if there is an ambient isotopy
between them (i.e. if one knot can be moved through space
smoothly, without passing through itself or being cut, so that it is
identical to the second.)
Knot theorists spend all their time trying to nd new invariants
which will tell apart knots.
Denition
Denition
Denition
I wonder if the trefoil is the same
as the figure eight knot...
How can I tell that the
Hopf link is really linked?
A KNOT THEORIST
I wonder if Dave will steal more
doughnuts this week...
NOT A KNOT THEORIST
What is the meaning
of life?
Crossing over to the dark side...
Knot theorists nd it easiest to study the 2-dimensional shadows
cast by the 3-dimensional knots.
The projection of a knot encodes all the information of the original
knot, so long as we know which crossings go over and which ones
go under.
For an oriented knot, we can give each crossing a sign depending
on which type it is:

+1

1
Crossing over to the dark side...
Knot theorists nd it easiest to study the 2-dimensional shadows
cast by the 3-dimensional knots.
The projection of a knot encodes all the information of the original
knot, so long as we know which crossings go over and which ones
go under.
For an oriented knot, we can give each crossing a sign depending
on which type it is:

+1

1
Example (The Trefoil)
1
Invaluable Invariants
With just the simple idea of signed crossings, we can already come
up with a few ways to tell apart knots.
The crossing number is the minimum number of crossings
over all possible projections of the knot.
The unknotting number of a knot is the minimum number of
crossing signs we must change to get to the unknot.
The writhe is the sum of the signs of the crossings (actually
not an invariant, but can be made into one).
For links, we have an invariant which is similar to the writhe.
The linking number of components J and K is the sum of the
signs of the crossings where J crosses K.
Unfortunately we now have to do a bit of boring Biology. Please:
Dont fall asleep.
Dont ask any dicult questions.
Dont criticise me if I pronounce things wrong.
Do play with the pretty knots in the room.
Dont fall asleep.
Dont fall asleep.
Dont fall asleep.
Dont fall asleep.
What is DNA?
DNA (Deoxyribonucleic acid) contains the genetic instructions
which tell living organisms how to function.
It does not act on other molecules, but instead is acted upon
by enzymes which copy its information into more DNA
(replication) or use it in protein synthesis (transcription).
DNA is usually tightly packed into cell nuclei, and must be
unpacked before the enzymes can act on it. Dierent enzymes
(topoisomerases) accomplish this feat of unpacking.
What is DNA?
What is DNA?
What is DNA?
The Structure of DNA
DNA consists of two strands twisted together
into a right-handed helix.
Attached to the sugar molecules in the strands
are four types of base, denoted A, T, C and G.
DNA can exist in linear form or in closed cir-
cular form. The circular form may be knotted,
and two or more DNA molecules may be linked
together.
What were those questions again?
1. How can knot theory help us to distinguish DNA molecules?
We can look at how the two strands of the DNA twist together by
examining the linking number.
Two DNA molecules might have the same sequence of base pairs,
but if the strands have dierent linking numbers then they will act
dierently.
In this case we call them stereoisomers.
dierently.
dierently.
Example
Linking Number = 3
Linking Number = 5
Supercoiling
2. How can knot theory help biologists to understand the ways in
As we said before, DNA is packed up tightly into cells - this is
called supercoiling.
Imagine twisting a rubber band or a telephone cord too many
times!
Theorem
Linking Number = Writhe + Twist
Supercoiling
times!
Theorem
Supercoiling
times!
Theorem
Supercoiling
times!
Theorem
Writhe=3
Writhe=0
Bring on the enyzmes!
If we want to do useful things with DNA (e.g. replication) then we
need to straighten it out a bit rst.
The enzymes which do this are called topoisomerases, and they
come in two varieties:
Those which are modest and only snip one strand of DNA at
a time (Type I)
Those which try to be clever and snip two strands at at a time
(Type II).
Bring on the enyzmes!
If we want to do useful things with DNA (e.g. replication) then we
need to straighten it out a bit rst.
The enzymes which do this are called topoisomerases, and they
come in two varieties:
Those which are modest and only snip one strand of DNA at
a time (Type I)
Those which try to be clever and snip two strands at at a time
(Type II).
Type II topoisomerases work by decreasing the writhe of
supercoiled DNA. They do this by changing a crossing from
positive to negative:
+
+ +
+
_
+
Writhe = 3
Writhe = 1
The fact that Type II can change crossing numbers has other
important applications. Sometimes two strands of DNA are linked
together, like the Hopf link:
For the DNA to replicate, these two links need to be separated. In
the case of the Hopf link, the enzymes can do this by changing just
one crossing:
The fact that Type II can change crossing numbers has other
important applications. Sometimes two strands of DNA are linked
together, like the Hopf link:
For the DNA to replicate, these two links need to be separated. In
the case of the Hopf link, the enzymes can do this by changing just
one crossing:
This brings us nicely onto our third question.
3. How can knot theory give us estimates of the rates at which
enzymes act on DNA?
The topoisomerase enzymes only have the power to change one
crossing at a time. Thus, if we know the unknotting number of a
link or knot this can give the biologists a good estimate of the time
taken for the enzymes to do their stu.
I have the power!
This brings us nicely onto our third question.
3. How can knot theory give us estimates of the rates at which
enzymes act on DNA?
The topoisomerase enzymes only have the power to change one
crossing at a time. Thus, if we know the unknotting number of a
link or knot this can give the biologists a good estimate of the time
taken for the enzymes to do their stu.
I have the power!
And one more thing...
Biologists have a big problem: they have no way of observing the
action of an enzyme.
What they do have is a technique called electrophoresis which can
separate molecules of dierent weights and shapes. Unfortunately,
the DNA molecules all have the same weight.
However, it turns out that this technique can also separate DNA
molecules according to how many crossings they have!
Therefore knowing the crossing numbers of knots helps biologists
to nd their molecules and see what the enzymes have done to
them.
them.
them.
Theyve gured out a clever way of coating the DNA in a special
protein which allows the crossing types to be easily seen.
Example
Theyve gured out a clever way of coating the DNA in a special
protein which allows the crossing types to be easily seen.
Example
What have we learnt?
Knot Theory is useful!
But that doesnt make me an applied mathematician...
Thank you for listening!
The obligatory bad joke...
A string walks into a bar and ask the waiter for a beer.
The waiter says, I am sorry but we cant serve strings here.
The string goes home, ties himself in a knot, and messes up his
hair. He goes back to the bar about an hour later, sits down and
says, Waiter, give me a beer.
The waiter says,Hey arent you the string who came in here
earlier.
The string replies, No, Im a frayed knot.

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Outline An Introduction to Knot Theory Some Biology revision Knotted DNA Conclusion

DNA, or knot DNA? That is the question.

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