Telomeres, Mitosis, and Cancer
For life to exist,
the information
(genes) must be
passed on.
Fig 3.5
The Cell Cycle
DNA replication
Fig 11.7
Sometimes
errors are
made.
Error
Luckily, errors
can be
repaired.
As they occur
by DNA
polymerase
Not all errors get repaired.
These are mutations.
Telomeres are non-gene DNA at the
ends of DNA strands.
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
Cycle
very little
telomerase
high levels of
telomerase
Why not
produce
telomerase
all of the
time?
very little
telomerase
high levels
of
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
Telomere length varies in
different parts of adults:
telomeres - mitosis
stomach &
blood cells....short - often
Telomere length varies in
different parts of adults:
telomeres - mitosis
stomach &
blood cells....short - often
muscle &
brain……….long - rare
Telomere length varies in
different parts of adults:
telomeres - mitosis
stomach &
blood cells....short - often
muscle &
brain……….long - rare
liver &
kidney……..short - rare
Telomere length varies in
different parts of adults:
telomeres - mitosis
stomach &
blood cells....short - often
muscle &
brain……….long - rare
liver &
kidney……..short - rare
gametes……long
Telomeres are non-gene DNA at the
ends of DNA strands.
Telomeres are more sensitive DNA damage,
and may act as a sensor for overall DNA
damage level in a cell.
Does telomere length indicate
longevity?
Telomere length in red blood cells of different birds
Zebra finch
Age (years)
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47
Telomere length in red blood cells of different birds
common tern
Age (years)
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47
Telomere length in red blood cells of different birds
albatross
TRENDS in Ecology and Evolution Vol 21 pg 47
Telomere length in red blood cells of different birds
Leach’s storm petrel
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47
Telomere length in red blood cells of different
birds, different species have different patterns
of telomere length and age
Zebra finch
common tern
albatross
Leach’s storm petrel
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47
Telomere length in white blood cells of
different aged people. Telomere length
generally declines, but there is wide variability
Fig. 2 TRENDS in Ecology and Evolution Vol 21 pg 47
proportion surviving %
Telomere length and mortality in people over
60 years old
upper 50%
of telomere
length
lower 50%
of telomere
length
years after initial assessment
THE LANCET • Vol 361 • pg 393
Telomere length may indicate
biological age.
Early stress may cause premature
telomere degradation.
{Meiosis:
producing gametes}
For life to exist,
the information
(genes) must be
passed on.
{Mitosis:
producing more cells}
Fig 3.5
The Cell Cycle
Mitosis:
A DNA
Perspective
Mitosis plays a role in:
• Growth and Development
• Repair and Turnover of Cells
• Reproduction
–Asexual
start
of
mitosis
Fig 3.8
Fig 3.7
The
Mitotic
Spindle
(microtubules)
A basic look at mitosis
Sister
Chromatids
Mitosis is tightly regulated: checkpoints
Fig 22.16
Cell division is regulated by both
positive and negative signals.
Positive signals start the process
of cell division.
Negative signals inhibit cell
division.
2 proteins, Cyclin and Cdk, control entry into mitosis
Fig
22.16
Fig 22.16
2 proteins, Cyclin
and Cdk, control
entry into mitosis.
Cdk
Balance between
Longevity and
Health
Fig. 3 TRENDS in Ecology and
Evolution Vol 21 pg 47
Mutations
Cancer: Cell Division Gone Wrong
Normal Mammalian
Cells Have
Contact Inhibition
Cancer Cells
Do Not Have
Contact Inhibition
Tumors in a Liver
normal
tumors
Cancer:
• is the loss of control over cell division.
• Tumors are normal cells that are
dividing inappropriately.
– They stop performing their “normal”
function, and are dividing repeatedly.
A cell becomes cancerous
when there are incorrect
positive AND negative
signals.
GO!
STOP!
cancer
Multiple mutations are
required for cancer to occur
Fig
22.17
Tbl 22.9
Tbl 22.9
Normal Cells
Cancer Cells
Benign versus Malignant cancer
How do these mutations arise?
Fig 22.18
Chromosome abnormalities in cancer cells
Causes of mutations:
• Replication errors
– Exacerbated by poor DNA repair
• Genetic predispositions for poor repair or already
having some mutations
– Limited by telomere length
Tbl 22.10
Causes of mutations:
• Replication errors
– Exacerbated by poor DNA repair
– Limited by telomere length
• Other biological agents
– Viruses
– Transposons
Causes of mutations:
• Replication errors
– Exacerbated by poor DNA repair
– Limited by telomere length
• Other biological agents
– Viruses
– Transposons
• Environmental factors
– Ultraviolet light
– Mutagenic chemicals
• smoking, industrial waste, natural toxins
Environment plays a large role in the chance of
contracting cancer…
The multiethnic cohort study: exploring genes, lifestyle and cancer risk. L Kolonel, D Altshuler, B Henderson (July
2004) Nature Reviews Cancer 4, 519-527 Fig 1