Applications of Topology to DNA
Muhammad Bilal (BSE21-47) Hussnain (BSE21-23) Zain Shahfique (BSE21-32)
Department of Mathematics, University Of The Punjab Lahore
1. Introduction
Topology, a branch of mathematics concerned with spatial properties and structures, finds various applications in the study of DNA molecules. This
poster explores the role of topology in understanding DNA structure, function, and analysis.
2. DNA Topology 4. DNA Packaging
DNA topology refers to the study of the spatial Topology plays a significant role in understanding how DNA is packaged within the cell nucleus. By
configuration of DNA molecules and their in- studying the spatial organization of DNA strands, researchers gain insights into gene regulation and
teractions. Topological concepts such as knots, chromatin structure.
links, and twists are used to analyze DNA struc- Differential geometry and DNA
ture and function. Lk = T w +W r, a well known formula in differential geometry, may be even better known in
molecular biology. The meanings of twist and writhe are probably best demonstrated with a belt.
3. Knot Theory and DNA While holding on to one end of the belt, twist the other end 180◦ for half a twist, 360◦ for 1 full
twist, etc. Twist describes how two strands (in this case, the two edges of the belt) wind about each
Knot theory provides mathematical tools for other in space. Now, without letting go of the twist, close up the belt. If you relax the belt, the
studying the entanglement of DNA molecules. twist is converted into writhe. If the belt is unknotted, writhe describes the amount of supercoiling.
Understanding DNA knots is crucial for unrav- Writhe measures how the center line of the belt winds around in space. It is defined to be the sum
eling the mechanisms of DNA replication, re- of all signed self-crossings of the center line averaged over all projections in R3 .
combination, and repair.
Some enzymes require DNA to be in a certain
configuration in order for the enzyme to act.
Electron micrographs of the enzyme-DNA com-
plex show the enzyme as a blob with DNA loop-
ing out of it. The configuration of the DNA
within the blob cannot be determined from the
EM. Thus, the mathematics of tangles has been
By moving the belt you are continuously converting writhe to twist and vice versa. Thus, these
used in many cases to determine the configura-
values are neither integers nor topological invariants. However, their sum, Lk, is both an integer and
tion of the DNA within the enzyme blob.
a topological invariant. The linking number is one-half the sum of all the signed crossings between
the two curves. DNA prefers a certain helical twist (10.4 base pairs/turn in the test tube). Therefore
changes in linking number are converted to writhe, i.e., the DNA becomes supercoiled. The more
supercoiled the DNA is, the more compact it is, and the faster it travels through a gel. Thus the
integer differences in linking number can be detected by gel electrophoresis.
The enzyme-DNA complex can be modeled by
writing the DNA as the numerator closure of the
sum of three tangles. The tangle Of represents
the free DNA, i.e., the part of DNA that is not For example, biologists used differences in linking number to determine that a mutant of Gin recom-
bound by the enzyme. Tangles Ob and P are binase was capable of relaxing supercoiled DNA and performing recombina-tion using more than one
both bound by the enzyme, but the enzyme only DNA configuration, whereas wild-type Gin can only perform recombination when the DNA is in one
affects the tangle P. Tangles Ob and Of do not specific configuration. This information gave insight into the enzyme mechanism as well. Linking
change during the reaction. differences have also been used to determine topoisomerase activity.
5. Topological Analysis Techniques
Various topological analysis techniques, such as persistence homology and loop space theory, are
used to study DNA structure at different scales. These techniques help uncover hidden patterns and
structures in DNA sequences and genomes.
Type 1 topoisomerases can only break a single backbone strand of DNA and thus can only change
The enzyme action is modeled by replacing tan- the topology of single-stranded DNA knots and links or double-stranded DNA knots and links if
gle P with tangle R. Many recombinase enzymes the double-stranded DNA contains a nick (a nick is a broken phosphodiester bond between the
act processively (i.e. it acts more than once sugars of two consecutive bases in one of the strands of dsDNA). Since topoisomerase substrate can
in the same place before releasing the DNA). be either double-stranded or single-stranded, the line drawings in this paper can represent either
This is modeled by adding on multiple R tan- double-stranded or single-stranded DNA, depending on context.
gles. Since the substrate and products of the
experiment are known, this gives several equa-
tions which can then be solved for some of the
unknown tangles:
6. Applications in Genetics
Topology has practical applications in genetics, including DNA sequencing, genome mapping, and
evolutionary biology. By applying topological methods, researchers can better understand the genetic
D. W. Sumne r s, C. E rn s t, S. Spen gle r and N. basis of diseases and develop novel therapeutic strategies.
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