AP Biology

Regulation of Cell Division

AP Biology

1.Coordination of cell divisiona. A multicellular organism needs to

coordinate cell division across different tissues & organsi. critical for normal growth,

development & maintenancea. coordinate timing of

cell division

b. coordinate rates of cell division

c. not all cells can have the same cell cycle

2

AP Biology

G2

S G1

Mmetaphase

prophaseanaphase

telophase

interphase (G1, S, G2 phases)mitosis (M)cytokinesis (C)

C

a. Frequency of cell division varies by cell typei. embryo

i. cell cycle < 20 minute

ii. skin cellsi. divide frequently throughout lifeii. 12-24 hours cycle

iii. liver cellsi. retain ability to divide, but keep it in reserveii. divide once every year or two

iv. mature nerve cells & muscle cellsi. do not divide at all after maturity

ii. permanently in G0

2. Frequency of cell division

3

AP Biology

3. Overview of Cell Cycle Controla. Two irreversible points in cell cycle

i. replication of genetic material

ii. separation of sister chromatids

b. Checkpoints i. process is assessed & possibly halted

centromere

sister chromatids

single-strandedchromosomes

double-strandedchromosomes

There’s noturning back,

now!

4

AP Biology

4. Checkpoint control systema. 3 major checkpoints:

i. G1/S1. can DNA synthesis begin?

ii. G2/M1. has DNA synthesis been

completed correctly?2. commitment to mitosis

iii. spindle checkpoint1. are all chromosomes

attached to spindle?2. can sister chromatids

separate correctly?5

AP Biology

5. G0 phase

MMitosis

G1Gap 1

G0Resting

G2Gap 2

SSynthesis

a. If signal is “NO” cell goes to G0 phase:

b. G0 phase1. non-dividing, differentiated state

2. most human cells in G0 phase

i. liver cells

a. in G0, but can be “called back” to cell cycle by external cues

ii. nerve & muscle cells

a. highly specialized

b. arrested in G0 & can never divide

6

AP Biology

a. How do cells know when to divide? i. cell communication signals

a. chemical signals in cytoplasm give cue

b. signals usually mean proteins

1. activators

2. inhibitors

6. Activation of cell division

experimental evidence: Can you explain this?7

AP Biology

7. Cyclin & Cyclin-dependent kinasesa. CDKs & cyclin drive cell from

one phase to next in cell cycle

1. proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conserved through evolution

2. the genes are basically the same in yeast, insects, plants & animals (including humans)

8

AP Biology

8. External signalsa. Growth factors

1. coordination between cells

2. protein signals released by body cells that stimulate other cells to dividea. density-dependent inhibition

I. crowded cells stop dividing

II. each cell binds a bit of growth factor

a. not enough activator left to trigger division in any one cell

b. anchorage dependence I. to divide cells must be attached to

a substrate

a. “touch sensor” receptors9

AP Biology

9. Cancer & Cell Growtha. Cancer is essentially a failure

of cell division control i. unrestrained, uncontrolled cell growth

b. What control is lost?i. lose checkpoint stops

ii. gene p53 plays a key role in G1/S restriction pointa. p53 protein halts cell division if it detects damaged DNA

1. options:a. stimulates repair enzymes to fix DNA

b. forces cell into G0 resting stage

c. keeps cell in G1 arrest d. causes apoptosis of damaged cell

b. ALL cancers have to shut down p53 activity

p53 discovered at Stony Brook by Dr. Arnold Levine

p53 is theCell CycleEnforcer

10

AP Biology

10. Development of Cancera. Cancer develops only after a cell experiences

~6 key mutations (“hits”)i. unlimited growth

i. turn on growth promoter genes

ii. ignore checkpointsi. turn off tumor suppressor genes (p53)

iii. escape apoptosisi. turn off suicide genes

iv. immortality = unlimited divisionsi. turn on chromosome maintenance genes

v. promotes blood vessel growthi. turn on blood vessel growth genes

vi. overcome anchor & density dependencei. turn off touch-sensor gene

It’s like anout-of-controlcar with many

systems failing!

11

AP Biology

11. What causes these “hits”? a. Mutations in cells can be triggered by

UV radiation chemical exposure radiation exposure heat

cigarette smoke pollution age genetics

12

AP Biology

12. Tumorsa. Mass of abnormal cells

1. Benign tumor 1. abnormal cells remain at original site as a

lump 1. p53 has halted cell divisions

2. most do not cause serious problems &can be removed by surgery

2. Malignant tumor cells leave original site

lose attachment to nearby cells carried by blood & lymph system to other tissues start more tumors = metastasis

impair functions of organs throughout body

13

AP Biology

13. Traditional treatments for cancersa. Treatments target rapidly dividing cells

i. high-energy radiation 1. kills rapidly dividing cells

ii. chemotherapy1. stop DNA replication2. stop mitosis & cytokinesis3. stop blood vessel growth

14

AP Biology

Any Questions??