Today

1
Todays lecture

• DNA makes RNA which makes Proteins
• Central Dogma of Molecular Biology Proteins
• DNAHow to measure its flexibility
• Magnetic Traps.
• Homework Schedule
• Turn in HW1 now.
• HW 2 Due Monday 2/4
• There will be a TA from 11-1115 in lecture rm,
  136 LLP to collect HW.
• HW3 will be assigned this Wednesday 1/13 Due
  Monday 2/11/13

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Minimal knowledge about NucleotidesMake up DNA
(also RNA)

• 4 nucleotides A,T,G,C (RNA U replaces T)
• AT 2kT two hydrogen bonds
• GC 4kT three hydrogen bonds
• From Homework, you know that one or a few A-T or
  G-C bonds will come apart, but have a series of
  them, and the two halves always stay together,
  i.e. are stable.

Each strand held together by covalent
bonds. (Stable) 3.4 Å/base
If DNA is very long, and have to unzip DNA, how
does this happen?
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Your DNA
You have 3 billion base-pairs, in 46 individual
sections, called a chromosomes. There are 23
pairs. An X from mother X or Y from father
(determines sex) Slight shuffling of 1-23
chromosomes, called meiosis, such that you are
different than the average of your parents.
1 meter in every cell!
Total Length DNA (3.4 Å)(3 x 109)
Nucleus of Cell 5 mm long
What does this tell you about the flexibility of
DNA?
Learn about Magnetic Traps to measure Persistence
Length.
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Most Biopolymers in Body are in Cells
Bacteria Prokaryotes (No nucleus)
Eukaryotic cell (us) (Has nucleus)



?10-100 mm?
?10-30 mm?
?1 mm?
(Nucleus 3-10 mm)
? 1014 (50-100 trillion!) cells in body more
stars than in Milky Way Galaxy.
Yet there are ? 200 different types of cells in
body. (Heart cell not equal to a brain
cell) Each type of cell is diff. cause diff.
parts of DNA is turned on.
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DNA is a double helix of anti-parallel strands
3.4 Å
3.4 nm per 10 base-pairs 1 turn (360º)
Must come apart for bases to be read.
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DNA? RNA? ProteinsCentral Dogma of Molecular
Biology
Double-stranded
Mostly single-stranded
Proteins linear series of 20 amino acids
Met-Ala-Val- each
coded by 3 bases ? amino acid AUG? Methionine
GCU ? Alanine GUU? Valine Proteins are 3-D
strings of linear amino acids Do everything
structure, enzymes
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How to make nucleotideAnother Example of
condensation reaction
Free H2O lots of entropy gained Reaction wants
to go.
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Covalent bonds holding bases together very
strong
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If add salt to solution, what is effect on
melting Temp? Melting temp Temp. at which DNA
strands come apart.
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DNA is twisted antiparallel for base pairing
Thymine
Cytosine
Hydrogen Bonds (2kT)
Guanine
Adenine
G-C more stable than A-T
Minor grove
Major grove

• p stacking keeps it together (Grease)
• Phosphate negative charge makes it water soluble
• (Sort of like soap)

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DNA ReplicationChicken Egg Problem
Have already shown that If DNA is long and
therefore very stable, how can it replicate
itself without an enzyme (to lower the activation
energy)? (Nowadays, it uses DNA polymerase, which
is an enzyme, i.e. protein.) The answer won a
Nobel prize! Involves RNA implications for the
start of life on earth.
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Difference between RNA and DNA is the Sugar 1
Base (T, U)
RNA is a string of nucleotides, just like DNA
? Larger groove (than DNA)more likely to be
attacked by enzymes)
RNA substitutes Uracil for Thymidine
Uracil will base pair with many groups. Methyl
group restricts uracil (thymine) to pairing only
with adenine.
Thymidine greatly improves the efficiency of DNA
replication, by reducing the rate of mismatches,
and thus mutations. Also, methylation protects
DNA from viruses.
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RNA can be its own enzyme!
RNA can be a ribozyme a ribonucleic acid and
enzymeis an RNA molecule with a well defined
tertiary structure that enables it to catalyze a
chemical reaction. It contains an active site
made completely of RNA. Can cut either itself or
another RNA.
http//en.wikipedia.org/wiki/Ribozyme
Used by nature! The ribosome, used to make
proteins from RNA, is itself a ribozyme (involves
RNA cutting by another RNA). 2009 Nobel Prize
(Ramakrishnan, Cambridge Steitz, Yale Yonath
Weizmann)
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RNA solves the chicken egg problemFrom Nobel
Lecture
The discovery of catalytic properties in RNA also
gives us a new insight into the way in which
biological processes once began on this earth,
billions of years ago. Researchers have wondered
which were the first biological molecules. How
could life begin if the DNA molecules of the
genetic code can only be reproduced and
deciphered with the aid of protein enzymes, and
proteins can only be produced by means of genetic
information from DNA? Which came first, the
chicken or the egg? Sid Altman and Tom Cech
have now found the missing link. Probably it was
the RNA molecule that came first. This molecule
has the properties needed by an original
biomolecule, because it is capable of being both
genetic code and enzyme at one and the same time.
Presentation Speech by Professor Bertil Andersson
of the Royal Swedish Academy of Science, December
10, 1989
RNA can be catalytic! Life probably started with
RNA (not DNA)
1989 Nobel PrizeAltman Cech (1967 Carle Woese
suggested RNA can be catalyticwon the equivalent
of Nobel Prize)
It is now possible to make ribozymes that will
specifically cleave any RNA molecule. These RNA
catalysts may have pharmaceutical applications.
For example, a ribozyme has been designed to
cleave the RNA of HIV. If such a ribozyme was
made by a cell, all incoming virus particles
would have their RNA genome cleaved by the
ribozyme, which would prevent infection.
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Evidence that RNA have these properties?
The Ribosome is an RNA-based catalytic machine
Big surprise!
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Magnetic Traps(see next section of slides)