BIOK101 Chapter 12 - Cell Cycle, Mitosis, Cancer

S phase

duplicated chromosomes

Copy of genome

sister chromatids

duplicated chromosomes

Genome

chromosome

chromatid

gene

Genome

46 chromosomes

After S Phase

2 identical sister chromatids

46 duplicated chromosomes

Mitosis

separate sister chromatids

Centrosomes

attach spindle fibres

Prometaphase

fragments of nuclear envelope

formation of microtubules

Binary Fission

single circular chromosome duplicated at the origin of replication for prokaryotes

dinoflagellates

nuclear envelope remains intact and spindle passess through nucleus

diatoms

nuclear envelope remains intact, spindle forms within nucleus

kinetochore microtubes

shorten at kinetochore ends during anaphase

tubulins emergent property

dynamic instability

microtubules depolymerize at kinetochore ends and release tubulin subunits

cell regulated

G1, S phase

“Stop” Checkpoints

G1

S

prometaphase

S phase promoting complex

go ahead signal to continue cell cycle

2 proteins regulating cell cycle

cyclin

cyclin dependent kinases

MPF

maturation promoting factor

MPF Maturation Promoting Factor

cyclin-Cdk

move cell past G2 into M phase

Dimer of Cyclin+Cdk

Cyclin concentration

increase during M phase

Cdk

stable levels throughout cell cycle, but activated by cyclin

cancer

normal checkpoints ignored transform onto cancer cell

Tumor

repreating uncontrolled mitosis

benign tumors

cells remain at original site

Malignant tumors

induce new blood vessel growth

angiogenesis

new blood vessel growth

metastasis

spread cancer cells

4 features of cancer features

1. replicative immortality

2. unusual karyotype

3. abnormal cell surface

4. ignore density dependent inhibition of growth

Replicative immortality

divide indefinitely if supplied with nutrients

active telomerase

unusual karyotype

different chromosome # or mutations

abnormal cell surface

cancer cells round up and break attachments

ignore density dependent inhibition of growth

multiply after contact with other cells until all nutrients are exhausted

biological hallmarks of cancer

sustaining proliferative signaling

evading growth suppressors

enabling replicative immortality

resisting cell death

inducing angiogenesis

activating invasion and metastasis

transformation

multi hit process, how cancer starts

oncogenes

switch on

Ras G protein

mutations causing gain of function

>30% of all cancers

p53 mutations

block cell divisions when errors in mitosis are found

>50% of all cancers

Gain of function oncogenes

go signals

excessive proliferation of cells

loss of function P53

lose stops signals, apoptosis, avoidance

Tumor heterogeneity

cancer cell within single tumor

not identical/vary in genetic makeup, different characteristics