The rest of the semester:

“DNA in motion”
Today: DNA Replication and Telomeres
Gene Expression is
regulated due to
environmental and
developmental cues:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 16.1
For life to exist,
the information
(genes) must be
passed on.
Fig 3.5

The Cell Cycle

DNA replication precedes cell division
 Fig 11.21

DNA
replication
starts at the
origin of
replication
 Fig 11.5

Prokaryotic origin of replication


• Other proteins such as HU and
IHF also bind.
– This causes the region to
wrap around the DnaA
proteins and separates the
AT-rich region
Fig 11.6
• DNA replication is initiated by the binding of
DnaA proteins to the DnaA box sequences
– This binding stimulates the cooperative
binding of an additional 20 to 40 DnaA
proteins to form a large complex
 Fig 11.6
Composed of six subunits
Travels along the DNA in the
5’ to 3’ direction
Uses energy from ATP

Bidirectional replication
 Fig 11.21
DNA
replication
starts at the
origin of
replication
Helicase unwinds/separates the two
strands of DNA.
 Fig 11.21

DNA
replication
The DNA is copied starts at the
origin of
replication
 Fig 11.21

DNA
replication
The DNA is copied starts at the
origin of
replication

More unwinding, more copying

 Fig 11.21

DNA
replication
starts at the
origin of
replication

The DNA has now been copied. There

are now two double-stranded DNAs
 DNA polymerase can only use some DNA as template
Completely single stranded
3' 5'
G A A T C T G C
Polymerase Fig 11.9
inactive

Completely double stranded

3' 5'
G A A T C T G C
Polymerase
inactive

C T T A G A C G
5' 3'
Single strand as template plus 3' end
to start synthesis
3' 5'
G A A T C T G C
Polymerase
active

C T T
5' OH
3'
 Fig 11.7

Primase adds an RNA primer to allow DNA

polymerase to begin
Fig 11.11

DNA polymerase
adds nuleotides
to the 3’-end
If DNA polymerase can only add nucleotides
to the 3'-end, how do both strands get copied?
Fig 11.10
How do cell’s stitch together Okazaki fragments?
Fig 11.10
 Fig 11.7
Proteins involved in DNA replication
 Fig 11.7
Some additional DNA replication
proteins
 Fig 11.7
DNA replication
Sometimes
errors are
made.
 Error

Luckily, errors
can be
repaired.
As they occur
by DNA
polymerase
 Fig 11.15

DNA polymerase has

3’-5’ exonuclease
activity
Fig 11.17
Fig 16.21
 Errors are made during DNA replication
3,000,000,000 (3 billion) base pairs/human cell
with
1 error/1 billion base pairs not repaired
= (average)
~6 errors each time DNA is replicated
Not all errors get repaired.
These are mutations.
Tbl 16.5

Common
causes of
mutations
Fig 16.4

Only mutations in
gametes will be
passed on.
How can mutations be minimized?
Telomeres are non-gene DNA at the
ends of DNA strands.
 Fig 11.23
• Telomeric sequences consist of
– Moderately repetitive tandem arrays
– 3’ overhang that is 12-16 nucleotides long

• Telomeric sequences typically consist of

– Several guanine nucleotides
– Often many thymine nucleotides
 Telomeres are non-gene DNA at the
ends of DNA strands.

Telomeres are shortened during DNA

replication.
 Fig 11.24
The problem of
replicating ends
Fig 11.25

Telomere lengthening
by telomerase
 Elongation of complementary telomere strand

Fig 11.25
The telomere forms a protective cap on the end
of the DNA with several cap proteins
 Telomeres are non-gene DNA at the
ends of DNA strands.

Telomeres are shortened during DNA

replication, and also by DNA damage.
 Telomeres are non-gene DNA at the
ends of DNA strands.

Short telomeres will cause cells to stop

replicating or cell death.

The critical size is unknown.

Human
Life
high levels of
Cycle telomerase

very little
telomerase
Why not
produce
telomerase
high levels
all of the of
time? telomerase

very little
telomerase
 Telomeres are non-gene DNA at the
ends of DNA strands.

Telomeres are shortened during DNA

replication, and by DNA damage.

Short telomeres will cause cell senescence or

cell death.
Telomere size is a measure of mutations.
Do telomere dynamics link lifestyle
and lifespan?

Pat Monaghan and Mark F.

Haussmann
TRENDS in Ecology and Evolution
Vol 21 pg 47