The Applet Version
runs directly off the web-browser and may be slower depending on the
internet connection. The Application Version can be downloaded to
the users hard drive and can be executed locally. Specific
directions for Windows and Unix can be located at How to Download Application Version.
is a web-band Java applet that runs in every
Most systems run full versions of Java. If not, the user may need
run the Applet Version. Or Java
run the application version.
Figure 1. Site-specific
recombinases fill the role of molecular scissors because they are able
cleave double-stranded DNA. In a single enzymatic event the enzyme
recognizes specific recombination sites, mediate a double-stranded break
at the core regions of each of the sites, recombines the lose ends, and
reseals the recombined strands as illustrated above.
TanlgeSolve is a Java computer program used
in the analysis of site-specific recombination.
Site-specific recombination is mediated by the protein site-specific recombinase and is important because of its key role in a wide
variety of biological processes such as: deoxyribose nucleic acid (DNA) rearrangement, integration and excursion of viral DNA into and out
of a host genome, and resolution of multimeric DNA molecules to allow proper segregation at cell division i.e. Tn3 resolvase (reviewed in
Ernst and Sumners (1990)) and Xer C and Xer D recombinases (reviewed in Vazquez et al (2004)).
Site-specific recombinases fill the role of molecular scissors (Figure 1) and are able to
change the topology of DNA by introducing double-stranded breaks at two specific DNA sites,
recombine the ends of the specific sites, and past the recombined sites' ends together.
This process can be considered to occur in two stages: synapsis and strand exchange. Synapsis, the first stage of recombination, is when
the recombination sites and accessory proteins on the same or different DNA substrate molecules are brought together globally prior to
recombination to form a specific synaptic complex. The bounded substrate and enzyme are also known as the pre-recombinant-DNA complex
(reviewed in Buck and Flapan (2007)). The second stage, strand-exchange, can be thought of as the recombination sites locally being
cleaved and exchanged. This is known as the post-recombinant complex (reviewed in Zheng et al (2000) and Vazquez et al (2004)). The
post-recombinant DNA molecule unbounded by the enzyme is known as the DNA product.
If the enzymes action is known (or believed) to act
processively, then TangleSolve will compute the solutions to the systems respectively. TangleSolve is an
interactive application which implements the Tangle Method and
offers an easy-to-use graphical interface for analyzing and visualizing
topological mechanisms of recombination. The Tangle Method
converts the biological problem of solving the enzymatic action into the
mathematical problem of computing the geometrical and topological
configuration of the DNA molecule before, during, and after the
recombination event. This is done by translating a recombination
event into a system of tangle equations. A
is a 3-dimensional ball with two non-self-intersecting arcs. The
Tangle Method finds solutions to tangle equations which are rational or
sums of rational tangles,
i.e. which can be easily wound and unwound by smooth
following example illustrates a tangle
equation and its graphical representation within TangleSolve:
N((0) + (2,2,2) + (0))
< 1,1,2,1,1 >
Figure 2. Standard knot diagram for 632*
from D.Rolfsen's Knots and Links
This program is concerned with site-specific
recombinases that converts unknotted
circular DNA substrates into knotted or linked DNA of specific
topology. TangleSolve assumes that substrates and products of recombination are 4-plats because most knots and links seen in biology are 4-plat
(or 2-bridge knots and links).
Given a link of specific substrate and
product topologies, TangleSolve finds all rational and sums of rational
tangle solutions to the corresponding system(s) of tangle
equations. The solutions are displayed as knot and tangle
diagrams as shown in Figure 3.
For a descriptive overview
of the mathematics and biology involved see Background
For an informative tutorial on how to use TangleSolve see Tutorial
Example of TangleSolve solution. Pictorally from left to right: numerator
addtion, knot or link illustration by D.Rolfsen, 4-plat.
please contact: firstname.lastname@example.org