Telomeres, Mitosis, and Cancer

For life to exist, the information (genes) must be passed on.

Fig 3.5

The Cell Cycle

Fig 11.7DNA replication

Sometimes errors are made.

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

Error

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.

HumanLifeCycle

high levels of telomerase

very little telomerase

Why not produce telomerase all of the time?

high levels of 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 lifestyleand lifespan?

Pat Monaghan and Mark F. HaussmannTRENDS in Ecology and Evolution

Vol 21 pg 47

Telomere length varies in different parts of adults:

telomeres - mitosisstomach &blood cells....short - often

Telomere length varies in different parts of adults:

telomeres - mitosisstomach &blood cells....short - often

muscle &brain……….long - rare

Telomere length varies in different parts of adults:

telomeres - mitosisstomach &blood cells....short - often

muscle &brain……….long - rare

liver &kidney……..short - rare

Telomere length varies in different parts of adults:

telomeres - mitosisstomach &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?

Zebra finch

Telomere length in red blood cells of different birds

Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47

Age (years)

common tern

Telomere length in red blood cells of different birds

Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47

Age (years)

albatross

TRENDS in Ecology and Evolution Vol 21 pg 47

Telomere length in red blood cells of different birds

Leach’s storm petrel

Telomere length in red blood cells of different birds

Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47

Zebra finch

Leach’s storm petrel

common tern

albatross

Telomere length in red blood cells of different birds, different species have different patterns of telomere length and age

Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg 47

Fig. 2 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

THE LANCET • Vol 361 • pg 393

Telomere length and mortality in people over 60 years old

upper 50% of telomere length

lower 50% of telomere length

prop

orti

on s

urvi

ving

%

years after initial assessment

Telomere length may indicate biological age.

Early stress may cause premature telomere degradation.

For life to exist, the information (genes) must be passed on.

{Mitosis:producing more cells}

{Meiosis:producing gametes}

The Cell CycleFig 3.5

Mitosis:A DNAPerspective

Mitosis plays a role in:• Growth and Development

• Repair and Turnover of Cells

• Reproduction

–Asexual

startofmitosis

Fig 3.8

TheMitoticSpindle(micro-tubules)

SisterChromatids

A basic look at mitosisFig 3.7

Mitosis is tightly regulated: checkpoints

Fig 22.16

Cell division is regulated by bothpositive and negative signals.

Positive signals start the processof cell division.

Negative signals inhibit cell division.

2 proteins, Cyclin and Cdk, control entry into mitosis

Fig22.16

Cdk2 proteins, Cyclin and Cdk, control entry into mitosis.

Fig 22.16

Fig. 3 TRENDS in Ecology and Evolution Vol 21 pg 47

Balance between Longevity and Health

Mutations

Cancer: Cell Division Gone Wrong

Normal Mammalian Cells Have Contact Inhibition

Cancer Cells Do Not Have Contact Inhibition

Tumors in a Livernormal

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

Fig22.17

Tbl 22.9

Tbl 22.9

Cancer Cells

Normal Cells

Benign versus Malignant cancer

How do these mutations arise?

Chromosome abnormalities in cancer cells

Fig 22.18

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