Math 414-714: Analyzing DNA topology with Mathematical and Computational Methods

Mariel Vazquez mariel@math.sfsu.edu Mathematics Department, SFSU

February 2nd, 2010 Mariel Vazquez - Math414-714: Lecture 3 1

2. Action of enzymes on DNA

recombination

Substrate

Products
(DNA knots or links)

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Mariel Vazquez - Math414-714: Lecture 3

Knots are spies

?
Substrate

recombination

Products
(DNA knots or links)

Goal: characterize the products experimentally; use Mathematics to elucidate the enzymatic mechanism.
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Experimental data

recombination

Substrate

Products (knots or links)

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Mariel Vazquez - Math414-714: Lecture 3

Tangle Model (Ernst and Sumners, 91)

Enzyme = ball .

Enzyme+bound DNA 2-string tangle 3-string tangle

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One round of enzymatic action is translated into a system of two tangle equations

recombination

N(O+P) = substrate N(O+R) = product

Where O, P and R are 2-string tangles

February 2nd, 2010

Mariel Vazquez - Math414-714: Lecture 3

Xer recombination
Experimental Data (Colloms et al., 1997)
(i) Substrate = unknotted DNA molecule (ii) Product = 4-crossing torus link Xer

Tangle Equations
(i) Substrate = N(O+P) = = <1> = = b(1,1)

(ii) Product = N(O+R) =

= <1,2,1> =

= b(4,3)

Solve for O and R.

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Results
Assuming P=(0) O = (-3,0) = and R= (-1) =

O = (-5,0) =

and R= (+1) =

O = (-4,0)=

and R=(0,0) =

Note: O is shown, mathematically, to be a rational tangle

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February 2nd, 2010

Mariel Vazquez - Math414-714: Lecture 3

Xer synapse: molecular model

M. Vazquez, S.D. Colloms, D.W. Sumners, J. Mol Biol (2005) 346: 493-504
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Computer implementation: TangleSolve

Java applet + Graphical user interface Location: http://bio.math.berkeley.edu/TangleSolve Saka Y. and Vazquez M., TangleSolve: topological analysis of sitespecific recombination, Bioinformatics (2002) 18:1011-1012

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February 2nd, 2010

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BaMBA meetings: Biology and Mathematics in the Bay Area

BaMBA I: SFSU BaMBA II: MSRI Berkeley BaMBA III: San Jose State University BaMBA IV UC Davis BaMBA V: UC Santa Cruz

BaMBA VI: November, 2010 Stanford University

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Other Activities
Chromatin research group and Journal Club: http://online.sfsu.edu/~pasion/cjc.html Math Biology Seminars, Math Department Center for Computing in the Life Sciences

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Chapter I: Atomic and Molecular Structure of DNA

Objective:
Describe the DNA molecule at the atomic level

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Section 1. Atomic interactions and Energy minimization

Today: 1.1 Basic facts about atomic structure 1.2 Atomic interactions and bond formation

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ATOMOS
An atom was defined by the greek as the smallest indivisible particle of matter. An atom consists of a nucleus surrounded by a cloud of electrons: nucleus : protons (+ charge); neutrons (neutral ch.) electron cloud: electrons (- charge) Def: If the number of protons in an atom equals the number of electrons then the atom is neutral; otherwise the atom is called an ion. Note: an accurate description of an electron and other atomic particles falls within the field of quantum mechanics, which is beyond the scope of our course. Intuitive Description
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Scales
Length: 1 nm =10=10-9 m Weight: 1 Dalton = 1.67 x 10-24 g = 1.67 x 10-27 kg Notation: 1 Dalton = 1Da = 1D Particle weight 1 e9.11x 10-28 g 1 proton 1.6929 x 10-24 g ~ 1D Approximation: 1 atom (#protons + #neutrons) x 1.6929 x 10-24 g ~ (#protons + #neutrons) D
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Scales in Molecular Biology

Length: (1 nm) =10A=10-9 m Weight: (1 Dalton): 1.67 x 10-24 g Water molecule Bacteriophage Escherichia coli (E. coli) Liver cell:
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0.3 nm

18D

25nm 4,700,000D 2,000nm=2m 2pg icrons 20microns 8 ng

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Mariel Vazquez - Math 414/714: Lecture 3

The Periodic Table (Mendeleev 1869)

IA IIA

Atomic number = Number of protons in the nucleus Period = horizontal row Group = vertical column
IIIA IVA VA VIAVIIA

VIIIA

Question: H has 1 proton, no neutrons, what is its mass?

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