Cell Cycle Regulation

What is the cell cycle?

A series of events within the cell that prepare it for division into two cells.

What are the five main phases of the eukaryotic cell cycle?

G1 (growth), S (DNA synthesis), G2 (chromosome condensation), M (mitosis), and C (cytokinesis).

Which phases make up interphase?

G1, S, and G2 phases.

What regulates the cell cycle?

Checkpoints that detect internal and external problems and send inhibitory signals.

Name the four main cell cycle checkpoints.

Restriction point (G1), DNA damage checkpoint (G1/S), DNA replication checkpoint (G2/M), and Spindle checkpoint (M).

What is the Restriction Point (G1)?

A checkpoint where the cell decides whether to proceed with division based on growth factors and conditions.

What was the experiment that led to the discovery of MPF?

Injection of cytoplasm from mature eggs (arrested in metaphase II) into oocytes in G2, inducing entry into M phase.

What does MPF stand for?

Maturation-promoting factor (also M phase-promoting factor).

What is MPF composed of?

A Cyclin and a Cyclin-dependent kinase (Cdk1/p34cdc2).

Who discovered cyclins?

Profs. Tim Hunt and Paul Nurse.

How were cyclins discovered?

By tracking newly synthesized proteins in fertilized sea urchin eggs; one protein accumulated during the cycle but was destroyed in mitosis.

What are cyclins?

Proteins that regulate the cell cycle by activating Cdks.

What are Cyclin-dependent kinases (Cdks)?

Enzymes that drive the cell cycle by phosphorylating target proteins.

How is cell cycle progression controlled?

By the relative levels of individual cyclins and their binding to Cdks.

Which cyclin binds during early G1 phase and to which Cdk?

Cyclin D binds to Cdk4 and Cdk6.

What does Cyclin D/Cdk4,6 complex do?

Phosphorylates the retinoblastoma protein (pRb) in mid-late G1.

Which cyclin acts in late G1 phase and which Cdk does it bind to?

Cyclin E binds to Cdk2.

Which cyclin acts in S phase?

Cyclin A binds to Cdk2 to allow exit from S phase.

Which complex regulates transition from G2 to mitosis?

Cyclin B/Cdk1 complex.

What happens at the G1 restriction point under nutrient deprivation?

Cells stop cycling in G1 phase if deprived of amino acids, serum, or phosphate.

What does the G1 restriction point monitor?

Cell size, environmental conditions, and interactions with neighbors and the matrix.

What does the microsurgery experiment on amoebae show?

Cells will not divide unless they reach a sufficient size.

What is the role of Retinoblastoma (Rb) protein?

Regulates the G1 restriction point of the cell cycle.

What genetic defect causes retinoblastoma?

A mutation in the RB1 gene on chromosome 13.

What is the significance of Rb in cancer?

Defects in Rb-mediated restriction point control are common causes of cancer.

What does the G1/S DNA damage checkpoint do?

Stops the cell cycle if DNA damage is detected.

What proteins detect DNA damage?

Sensors activate transducers, which act on effectors to block cell-cycle progression.

What does the G2/M checkpoint do?

Delays entry into mitosis until all DNA is fully replicated and undamaged.

What does the metaphase spindle assembly checkpoint ensure?

That chromosomes are properly attached to spindle fibers before anaphase begins.

What proteins compose the mitotic checkpoint complex (MCC)?

BubR1, Bub3, Mad2, and Cdc20.

What happens if a chromosome is not properly attached to the spindle?

The cell does not enter anaphase.

What is the role of APC (anaphase-promoting complex)?

A ubiquitin ligase that promotes chromosome segregation and mitotic exit by degrading securin.

What is securin?

A protein that prevents premature separation of sister chromatids; it is degraded by APC during anaphase.

What is aneuploidy?

An abnormal number of chromosomes in daughter cells.

What causes aneuploidy?

Errors in chromosome segregation during meiosis or mitosis.

What is the chromosomal cause of Down syndrome?

An extra copy of chromosome 21 due to nondisjunction during meiosis.

Why is maintaining chromosome number important?

To preserve the cell’s identity and proper function after division.