BM1- cell cycle regulation and growth control EXAM3

Why do cells divide?

Growth, replacement, tissue repair/wound healing

Why do cells divide for growth?

To make more cells

Why do cells divide for replacement?

To maintain normal tissue

Why do cells divide for tissue repair/wound healing?

To replace damaged cells

How often do cells divide?

Never, rarely, frequently, every 20 min, indefinitely

What does it mean when cells never divide?

They are terminally differentiated

Give 3 examples of terminally differentiated cells.

Neurons, myocytes, osteocytes

What does it mean when cells rarely divide?

They are reversibly quiescent

Give 4 examples of reversibly quiescent cells.

Stem cells, hepatocytes, thyroid cells, glial cells

How often do epithelial and bone marrow cells divide?

Every 12–24 hours

What is the Hayflick limit?

Most cells divide 20–50 times before dying

How often do embryonic cells divide?

About every 20 minutes

Which cells can divide indefinitely?

Cancerous cells or immortalized cultured cells

What influences adaptive responses to environmental stimuli?

Replicative capacity

What are the two types of growth signals?

Internal and external

What are examples of internal signals?

Kinases and phosphatases

What are examples of external signals?

Growth factors, direct cell contact, surface signals

How do external factors control the cell cycle?

They bind to receptors and trigger signaling pathways

What is the cell cycle?

A controlled sequence where a cell duplicates its genome, doubles content, and divides into two identical daughter cells

What are the two main phases of the cell cycle?

Interphase and mitosis

Which phase of the cell cycle is long and non-dividing?

Interphase

Which phase of the cell cycle is short and dividing?

Mitosis

What is the role of interphase?

Prepares the cell for mitosis

What happens during G1 phase?

Cells grow, metabolically active, RNA & protein synthesis

What happens during S phase?

DNA replication; DNA content doubles

What happens during G2 phase?

Protein synthesis for division, centrosome duplication

What happens during mitosis (M phase)?

Chromosomes replicate and divide equally between daughter cells

What is equatorial division?

Equal chromosome separation between daughter cells

What is karyokinesis?

Separation of chromosomes (4 stages)

What is cytokinesis?

Division of the cytoplasm

What happens to chromosomes in prophase?

Duplicated sister chromatids condense

What happens to the cytoskeleton in prophase?

Disassembles; microtubules form mitotic spindle

What happens to the nuclear envelope and nucleolus in prophase?

They disintegrate

What happens to centrosomes in prophase?

They move to opposite poles

What attaches to kinetochores in metaphase?

Spindle fibers

Where do chromosomes line up in metaphase?

At the equator of the spindle (metaphase plate)

What is a kinetochore?

Protein structure (>100 proteins) on centromeres for spindle attachment

Why must sister chromatids bind to microtubules?

For correct segregation

How are microtubules anchored in metaphase?

Minus ends at poles; plus ends at kinetochores

What happens to centromeres in anaphase?

They split

What happens to sister chromatids in anaphase?

They separate

How do chromatids move to opposite poles?

Shortening of spindle fibers

Where do chromosomes move in telophase?

Cluster at opposite poles

What happens to the nuclear envelope in telophase?

Reassembles around chromosome clusters

What happens to the nucleolus and organelles in telophase?

They reform

What ring appears in telophase?

Contractile ring

What forms the cleavage furrow in cytokinesis?

Actin and myosin microfilaments

What does the cleavage furrow deepen into?

Thin intercellular bridge called the midbody

What is the final result of cytokinesis?

Two separate daughter cells

What are checkpoints in the cell cycle?

Binary switches and surveillance mechanisms

What do checkpoint pathways consist of?

Event sensors, signaling pathway, effector

What does the effector in a checkpoint pathway do?

Halts cycle progression and activates repair mechanisms

Which checkpoint is the most important and rate-limiting?

G1 checkpoint (restriction point)

What 4 factors are checked at the G1 checkpoint?

Cell size, nutrients/energy, molecular cues, DNA integrity

What happens if a cell passes the G1 checkpoint?

“GO” → proceeds to S phase

What happens if a cell fails the G1 checkpoint?

“STOP” → moves to G0 (non-dividing, working state)

What does it mean for a cell to be in G0?

It has exited the cell cycle

What does quiescent mean in G0?

Cells can re-enter the cycle if they receive appropriate signals

What does senescent mean in G0?

Old cells permanently withdrawn from the cell cycle

What does terminally differentiated mean in G0?

Fully functioning cells withdrawn permanently from the cycle

What does the G2/M checkpoint check for?

Ensures DNA replication is finalized and checks for DNA damage

What happens if the cell passes the G2/M checkpoint?

“GO” → proceeds to mitosis

What happens if the cell fails the G2/M checkpoint?

“STOP” → triggers apoptosis

What does the spindle checkpoint ensure?

Chromosomes are properly attached to microtubules

What must chromatids be ready for at the spindle checkpoint?

Separation

What happens if the spindle checkpoint fails?

“STOP” → apoptosis

What controls cell cycle progression?

Cyclic synthesis and degradation of cyclins

What are cyclins?

Catalytic subunits of cyclin-dependent kinases (Cdks)

What do active Cdks do?

Phosphorylate and activate proteins during checkpoint transitions

What obscures the active site of Cdk when inactive?

The T-loop

How does cyclin binding affect Cdk?

Removes blockage of the active site → partial activation

What does phosphorylation of Cdk cause?

Conformational change → full activation

What do CKIs (cyclin kinase inhibitors) do?

Bind cyclins/Cdks, distort active site, inhibit enzymatic activity

Do cells in G0 synthesize cyclins or Cdks?

No

What is the role of Rb (retinoblastoma protein) in G1?

Blocks progression through cell cycle by binding E2F

What stimulates G1-Cdks in G1 phase?

Growth factors (mitogens)

How do growth factors (mitogens) promote cell cycle progression?

They stimulate G1-Cdks to phosphorylate Rb, releasing E2F

What happens when E2F is released?

Stimulates transcription of G1/S phase Cdks

What do G1/S phase Cdks promote?

Passage through the G1 checkpoint and initiation of DNA replication

What is the S-phase Cdk complex called?

SPF (S phase promoting factor)

What does SPF phosphorylate?

Helicase

What does phosphorylated helicase do?

Recruits helicase activators to origins of replication

What enzymes are recruited to initiate DNA replication in S phase?

DNA polymerases

What are mitotic cyclin-Cdk complexes also called?

MPF (Mitosis Promoting Factor)

When is MPF produced?

During G2

What does Wee1 kinase do?

Inhibits MPF until DNA replication is complete

What does Cdc25 phosphatase do to MPF?

Dephosphorylates and activates MPF (reverses Wee1 inhibition)

What happens at the end of mitosis to cyclins?

MPF activates APC/C, which degrades mitotic cyclins via ubiquitination

What holds sister chromatids together?

Cohesins (SMC1 & 3)

What enzyme separates sister chromatids?

Separase

How is separase activity controlled?

Inhibited by Cdk phosphorylation

What happens when the spindle (M) checkpoint is passed?

APC/C ubiquitinates mitotic cyclins → separase cleaves cohesins → chromatids separate

What kinases detect DNA damage?

ATM (single-strand breaks) and ATR (double-strand breaks)

What tumor suppressor gene is stabilized by DNA damage response?

p53

What happens when p53 is activated?

Activates p21 and induces cell cycle arrest

What are the two possible outcomes after DNA damage?

DNA repair or apoptosis