DNA Replication (Copying DNA Prior to Cell Division) (movies)

DNA Replication
(Copying DNA Prior to Cell Division)
(movies)
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http://www.dnai.org/a/index.html
Why high expectations are a good thing.
Today’s goals:
1) What is nanoscale in biology? Scale down
through the human body to get an idea.
2) Complexity: What has to be done to replicate
DNA? Next time transcription and translation
3) A picture of the nanoscale machines that pull off
these feats.
4) Periodic questions for the class to get a collective
answer: distance between base pairs in DNA
double helix? How many bases must be copied
to make an adult human? How do we know that
DNA replication isn’t perfect?
SIZE SCALE
The human body is about
1-2 meters in height
Scale down factors of ten
1meter nerves
1million cells
1 meter blood
vessels
10 cm
1 cm
.1 cm
= 1mm
.01 cm
= 100 um
A capillary and red blood cells
(movie)
10 um
Red blood cell
capillary
QuickTime™ and a
YUV420 codec decompressor
are needed to see this picture.
100 um
http://www.asahi-net.or.jp/~qw9m-mnmy/micmov01.mpg
5-10 um
white blood cell
2 um
red blood cell
capillary endothelial cell
Rhodes University
http://www.ru.ac.za/administrative/emu//gr10p4.htm
23 Chromosomes from each parent (46 total)
Cytoplasm
Nucleus
DNA
Alberts Figure 4-20
B. Hamkalo
V. Foe
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DNA Fibers
Photo 51,
Franklin
Watson & Crick
Nature, 1953
Alberts Figure 4-3
Alberts Figure 4-5
SCALE: NUMBER OF CELLS & COMPLEXITY
The Human Body
Number of cells and
their complexity
http://www.visembryo.com/baby/
http://www.visembryo.com/baby/
Day 1
Fertilization
Zygote Development
http://www.visembryo.com/baby/
Day 5
Blastocyst
The Human Body
100+ trillion cells
(50,000,000 replaced as
you read this sentence)
200-300 cell types
23 Chromosomes from each parent (46 total)
Cytoplasm
Nucleus
DNA
Scale of the replication problem: How much DNA
is copied?
Cytosol
Nucleus
DNA
•23 Chromosomes= 1 genome= 3 billion bases
• 2 sets of chromosomes (one from each parent)
• 2 strands per DNA duplex
Cytosol
Nucleus
DNA
12 billion bases
copied in one
cell division!
Cytosol
Nucleus
DNA
Alberts Figure 4-8
100 trillion cells
1 cell
Zygote
50 trillion cell
divisions
50 trillion cell divisions X 12 billion DNA bases replicated
cell division
= 600 Sextillion bases that must be accurately copied
1) How big is 600 sextillion?
Answer: 6 X 1024
(Stars in the visible universe = 7 X 1023)
WHAT MOLECULAR MACHINE CAN ACHIEVE THIS
REPLICATION SPEED AND FIDELITY?
Drew Berry (Aussie computer animator)
DNA Replication
(Copying DNA Prior to Cell Division)
(movies)
QuickTime™ and a
Animation decompressor
are needed to see this picture.
QuickTime™ and a
Animation decompressor
are needed to see this picture.
http://www.dnai.org/a/index.html
DNA Replication (Copying DNA Prior to Cell Division):
1) Unwind with a helicase
DNA Helicase (unwinds duplex)
Alberts Figure 5-16
DNA Replication (Copying DNA Prior to Cell Division):
2) Copy the leading strand with a polymerase
DNA polymerases
(make copies)
DNA polymerases are often described as a right hand
DNA Replication (Copying DNA Prior to Cell Division):
2b) holding the polymerase on with a sliding clamp
DNA polymerases
(make copies)
Holding the polymerase on
with a sliding clamp
Alberts Figure 5-19
DNA Replication:Review the leading strand
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The intuitive and logical approach that torpedoed
many careers a few decades ago
Alberts 5-7
What actually happens: Okazaki fragments
Alberts Figure 5-13
Alberts Figure 5-12
DNA Replication
(Copying DNA Prior to Cell Division)
(movies)
QuickTime™ and a
Animation decompressor
are needed to see this picture.
QuickTime™ and a
Animation decompressor
are needed to see this picture.
http://www.dnai.org/a/index.html
How long does it take to replicate a bacterial (E. coli)
genome?
1) 4.6 million base-long
circular chromosome.
2) 1000 bases added per
second.
3) Two replisomes work
In opposite directions from
replication origin.
Figure 5-6
How do we know DNA replication is not perfect?
1)Changes in DNA sequence (copying mistakes)
drive evolution.
2) Cancer often begins as a single cell that has
accumulated 3-5 base substitutions in critical genes.
Bert Vogelstein
video later this
Summer?