Chapter 18 - The Cell Cycle

What is cell division?

Nuclear replication plus cell division

What is cell division without nuclear division

Meiosis

What are the two phases of the cell cycle?

Interphase and M-phase

What are the stages of interphase?

G₁, S, G₂

What are the stages of M-phase?

Prophase, Metaphase, Anaphase and Telophase

How can the cell cycle be visualized?

Flow cytometry with fluorescent DNA

Are there more cells present in the G1 or G2/M phase?

G1

What stage of interphase contains the most amount of DNA per cell?

G2/M

What is the G₀ phase?

When cells exit cell cycle and become quiescent

What is quiescence?

Inactivity or dormancy of cell division

What is an example of quiescence in the body?

The liver cells start dividing when you drink to replace old liver cells

What checkpoints do cells go through when entering mitosis?

Is all DNA replicated? Is all DNA damage repaired?

What checkpoints do cells go through when in mitosis?

Are all chromosomes properly attached to the mitotic spindle?

What checkpoints do cells go through when entering S phase?

Is environment favorable?

Purpose of RTK

Growth factor receptor activates gene expression of cell cycle receptor

What is MPF (M-phase promoting factor)?

Stimulates mitosis in quiescent cells

What does cyclin concentration in a cell correlate to?

MPF activity

Where is MPF activity highest in the cell cycle?

M phase

What is the cell cycle control system dependent on?

Cyclically activated protein kinases (Cdk)

What is necessary for cdk to be fully activated?

Inhibitory phosphatases must be removed

What is the protein family that regulates what reproductive phase the cell is in?

Cyclins

How is the cell cycle control system dependent on proteolysis?

Cyclin is quickly recognized for breakdown through M phase so enzymes tags these cyclins with a chain of ubiquitin so that cdk can return to its inactive state

Why is it necessary for cyclins to be degraded and cdk to become in active in the cell cycle?

to progress to the next stage of the cycle and make sure cells don’t get stuck in one phase

How does S-Cdk play a role in regulating DNA replication?

It helps block the re-replication of DNA

How do mitogens stimulate cell proliferation?

By inhibiting Rb protein so without mitogens, dephosphorylated Rb holds transcription regulators in an inacitve state. Inhibition of Rb renders cell proliferation active.

What can Rb not bind to anymore when phosphorylated?

Transcription factor E2F which transcribes mitosis genes

How can the cell cycle be halted? Why is it important?

p27 inhibits cyclin/cdk so that when there is DNA damage, cyclin/cdk inhibitors are produced so that cells aren’t dividing while damage is being repaired.

What is the function of p21?

It blocks the assembly and action of cyclin/cdk’s which makes it a cdk inhibitor which halts the cell cycle for DNA repair

What pathway is induced when DNA damage occurs?

p53 phosphorylated → p21 expression → cell cycle stops

What is p53 and cdki’s?

tumor supressor proteins

What is programmed cell death?

Apoptosis, when cells are damaged beyond repair they die willingly

In what two ways do cells die?

1. Necrosis: random cell decay (gangrene)

2. Systematic dismantling of cell components

How are apoptitic cells removed?

they produce “blebs” called exosomes that break apart into small pieces so that phagocytic cells can eat them

What does cytochrome C leakage lead to?

Caspase cascade

What is caspase?

Proteases that cleave peptides

Why do our bodies produce more nerve cells than we need?

To ensure sufficient connections are formed

Why do nerve cells undergo apoptosis?

To reduce redundancy

Why do animal cells produce survival factors?

To avoid apoptosis

How do survival factors regulate Bcl2?

by influencing the expression and activity of pro-survival and pro-apoptotic members of the Bcl-2 family

What is the Bcl2 family?

Anti-apoptitic proteins and pro-apoptitic proteins

What is the extrinsic mechanism of apoptosis?

Extracellular signals bind to death receptors to trigger pro-apoptitic factors like tumor necrosis factors (TNF)

What is cellular senescence?

The permanent inactivation of proliferation after programmed number of divisions

Why do we age?

Our somatic cells can only divide a certain number of times so this limits the tissue regeneration and longevity abilities

What are the exceptions to programmed number of divisions?

Gametophytes, stem cells, gut lining, and skin

How to telomeres play a role in humans living so long?

They are the protective end caps of chromosomes and protect against gene loss

What happens when telomeres get critically short?

Tumor supressor proteins are activated which inhibit cell division

How do germ cells and stem cells maintain telomeres?

Through the activation of telomerase

How does the reactivation of telomerase cause cancer?

contributes to uncontrolled cell proliferation by maintaining telomere length and circumventing normal cellular limitations

What is cdk activity regulated by? (4)

• Cyclin synthesis

• Phosphorylation/Dephosphorylation

• Cyclin proteolysis

• Cdki

What is the initiation of mitosis called?

Prophase and mitogenesis