LESSON 5 Flashcards by mork .

A multicellular organism needs to coordinate _____ across different tissues & organs

cell division

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critical for normal growth,
development & maintenance

cell division

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not all cells can have the same ____

cell cycle

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____ of cell division varies by cell type

Frequency

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embryo
- cell cycle < ______

20 minute

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skin cells
- divide frequently throughout life ________cycle

12-24 hours

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liver cells
- retain ability to divide, but keep it in reserve divide once every _________

year or two

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cell cycle 20mins

embryo

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12-24 hrs cycle

skin cell

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divides only once or twice a year

liver cells

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do not divide at all after maturity permanently in G0

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Two irreversible points in cell cycle

replication of genetic material
separation of sister chromatids

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process is assessed & possibly halted

Checkpoints

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cell cycle controlled by STOP & GO chemical signals at critical points

checkpoints

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signals indicate if key cellular
processes have been completed correctly

checkpoints

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3 major checkpoint

G1/s, g2/m, spindle fiber scheckpoint

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can DNA synthesis begin?

`g1/s checkpoint

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has DNA synthesis been completed correctly?

g2/m checkpoint

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commitment to mitosis

g2/m checkpoint

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are all chromosomes attached to spindle?

spindle checkpoint

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can sister chromatids separate correctly?

spindle checkpoint

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primary decision point
- “restriction point”

g1/s checkpoint

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if cell receives “GO” signal, it _____

divides

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internal signals: ______, ______

cell growth (size), cell nutrition

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external signals: “____-______”

growth factors

if cell does not receives signal, it exits cycle & switches to _______________

G0 phase

non-dividing, working state

g0 phase

non-dividing, differentiated state

g0 phase

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

liver cells

highly specialized - arrested in G0 & can never divide

nervous & muscle cells

chemical signals in cytoplasm give cue

activation of cell division

signals usually mean proteins

activators , inhibitors

internal signals - “__________” external signals - “_________”

promoting factors growth factors

protein that regulate the metabolism, proliferation, apoptosis, subcellular trafficking, inflammation and other important physiological process.

phosporylation

primary mechanism control

phosporylation kinase enzymes - either activates or inactivates cell signals

checkpoints who

Leland H Hartwhell

Cdks who

Tim Hunt

cyclins who

Sir Paul Nurse

Growth factors Nutritional state of cell Size of cell

Cdk/G1 cyclin

Replication completed DNA integrity

Cdk/G2 Cyclin (MPF)

MPF

Mitosis Promoting Factor

Chromosomes attached at metaphase plate

APC (spindle scheckpoint)

APC

Anaphase Promoting Complex

normal growth factor genes that become oncogenes (cancer-causing) when mutated

proto-oncogenes

stimulates cell growth

proto-oncogenes

if switched “ON” can cause cancer

proto-oncogenes

- example: RAS (activates cyclins)

proto-oncogenes

inhibits cell division

tumor-supressor genes

if switched “OFF” can cause cancer

tumor-suppressor genes

example: p53

tumor suppressor genes

_____ is essentially a failure of cell division control

Cancer

unrestrained, uncontrolled cell growth

cancer

gene ___ plays a key role in G1/S restriction point

p53

____ protein halts cell division if it detects damaged DNA

p53

ALL cancers have to shut down _____ activity

p53

____ is the Cell Cycle Enforcer

p53`

p53 discovered at Stony Brook by _________

Dr. Arnold Levine

6 KEY MUTATION HITS

unlimited growth ignore checkpoints escape apoptosis immortality which means unlimited divisions promotes blood vessel growth overcome anchor & density dependence

- turn on growth promoter genes

unlimited growth hit

- turn off tumor suppressor genes (p53)

ignore checkpoints hit

- turn off suicide genes

escape apoptosis hit

turn on chromosome maintenance genes

immortality hit

turn on blood vessel growth genes

promote blood b=vessel growth hit

turn off touch-sensor gene

overcome anchor & density dependence

What causes these “hits”?

UV radiation chemical exposure radiation exposure heat cigarette smoke pollution age genetics

abnormal cells remain at original site as a lump

benign tumor

p53 has halted cell divisions

benign tumor

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

benign tumor

cells leave original site

malignant tumor

lose attachment to nearby cells - carried by blood & lymph system to other tissues

malignant tumor

start more tumors

malignant tumor

start more tumors

metastasis

impair functions of organs throughout body

malignant tumors

- kills rapidly dividing cells

high-energy radiation

stop DNA replication - stop mitosis & cytokinesis - stop blood vessel growth

chemotherapy