Ch. 24 - Cell Cycle

List the 3 main ideas of the Cell Theory

1. All living things come from cells

2. Cells are basic units of life

3. Cells come from pre-existing cells

What are the 2 Types of Cell Division in Eukaryotes? What do they produce?

• Mitosis: Produces 2 genetically identical diploid daughter cells (somatic)

• Meiosis: Produces 2 genetically unique haploid gametes (egg and sperm)

What are the 3 main purposes of Mitosis

1. Growth (single zygote → trillions of cells)

2. Wound Repair (replenish damaged tissue)

3. Asexual Reproduction

List and Breifly Explain the components of the Cell Cycle OVERVIEW. (List their Duration)

• G1 phase: Primary/majority growth phase. Cell size increases and preps for DNA synthesis (Longest 20-24 hrs)

• S phase: DNA replication occurs, chromosomes are duplicated but remain uncondensed AKA euchromatin state (2nd Longest Time)

• G2 phase: Secondary growth, cell preps for mitosis. Includes maturation of centrosomes and organelle synthesis (2-4 hrs)

• M phase & C phase: Mitosis and Cytokinesis takes place → producing 2 daughter cells. (<1 hr)

__________ consists of G1, S, and G2 phases. Characterized by growth and DNA replication before Mitosis.

• During G1 and S phases the Chromosomes are in a _______ state allowing enzyme access for replication.

Inter-phase

• euchromatic (uncondensed)

The Replicated Chromosomes consists of…

2 sister chromotids joined together by a centromere that has a kinetochore on it.

What is a Kinetochore?

A protein structure attachment site for spindle fibers to pull the sister chromotids apart.

At the end of G2 and During M Phase, chromosome become __________ (hetrochromatic), facilitated by the protein _______.

• Why is this protein important?

highly condensed; condesin

• makes chromosome movement easier & prevents breakage

Explain Prophase of Mitosis

Chromosomes condense & spindle apparatus starts forming (spindles form from centrosomes to poles); Nucleolus disappears

Explain Prometaphase of Mitosis

Nuclear envelope & lamina breaks down = spindle MT can access chromosomes. Kinetochores form at Centromeres.

Explain Metaphase of Mitosis

Chromosome align at the Metaphase plate, attach to spindle MT’s; Spindle Apparatus is fully formed

Explain Anaphase of Mitosis

Shortest mitosis phase driven by motor proteins for movement

• Sister chromotids separate and move to opposite poles (Anaphase A).

• Cell elongates as spindle poles move apart (Anaphase B).

In Anaphase specialized _______ help de-polymerize the MT at both ends puling chromotids apart. The Cell elongates as polar MT’s slide apart, which is pushed by _______.

• Astral MT anchor spindle pole positioning via…

Kinesin motor protein; Bipolar kinesin motors

• via Cytoplasmic Dyenin Motor Proteins

Explain Telophase of Mitosis

Nuclear Envelope reappears, chromosomes decondense, spindle breaks down → cell preps for Cytokinesis

Explain Cytokinesis of Mitosis

Cells cytoplasm divides → forms 2 daughter cells.

• In animal cells, a cleavage furrow forms via actin-myosin contraction

The Formation of the cleavage furrow is mediated actin filaments and myosin motor proteins. What is used at the Cleavage furrow to regulate actin polymerization and myosin activity?

• This component activates ______ for actin filament assembly.

• This component activates ______ to stimulate myosin II for contraction.

GTPase RhoA

• formin

• ROCK kinase

List the Components of the Spindle Apparatus (include the types of MT’s)

• Centrosomes: contains the centrioles and pericentriolar material

3 Types of MT’s

1. Kinetochore MT: Attach to kinetochores to facilitate movement

2. Polar MT: Extend toward cell center, overlap, and push spindle poles apart → elongating the cell

3. Astral MT: Anchor centrosomes to the cell cortex → helps position the spindle and cell shape via Cytoplasmic Dyenin Motor Proteins

Kinetochore structures are composed of…

• This has centromeric DNA that contains _______ which vary by species, and it's H3 histone is replaced by ________ at the centromeres to facilitate kinetochore assembly

Inner Kinetochore Plate: Binds to centromeric DNA

Outer Kinetochore Plate: Binds to Kinetochore MT’s; and contains motor proteins

• Tandemly repeated CEN sequences; centromeric proteins (CENP-A)

What is Taxol?

A Chemotherapy drug that stabilizes MT preventing their polymerization = inhibits Anaphase, cell division (in cancer cells)

The Cell cycle consists of the G1, S, G2, and M phases. Progression through these are directional and ________.

• Why is that?

irreversible

• once DNA replication occurs the cell cannot revert

Explain how the cell cycle is closely monitored.

It’s monitored via checkpoints to prevent errors. These checkpoints act as quality control mechanisms for the cells, monitors cellular conditions and signals to halt/permit progression

What are the 3 Major Cell cycle checkpoints?

1. G1 to S Phase transition AKA restriction point or start point

2. G2 to M Phases transition

3. Metaphase to Anaphase transition during mitosis AKA spindle checkpoint

What are Cyclin-Dependant Kinases (CDK)?

• CDK's require binding to regulatory proteins called _____ to become active. These are termed ________.

Enzymes that phosphorylate target proteins to regulate cell cycle progression.

• cyclins; cyclin-CDK complexes

The activity of cyclin-CDK complexes depends on…

• Presence of cyclins (these levels fluctuate)

• Phosphorylation status controlled by kinases and phosphatases

• Specific binding of inhibitors

Studies in frog oocytes revealed cytoplasmic factors controlling meiotic entry termed _______.

• This is a complex of ________, responsible for triggering progression from G2 to M phase

Maturation Promoting Facter (MPF)

• Cyclin B and CDK1

With peak activity at G2 to M transition, MPF promotes critical mitotic events such as…

• Breakdown of Nuclear Envelope

• Chromosome Condensation

• Spindle Formation

• Initiation of Protein degradation pathways through Anaphase-promoting complex (APC)

Explain the Process of the G2 to M Phase Checkpoint

1. the cyclin B-CDK1 complex is initially inactive due to inhibitory phosprlation

2. CDC25 removes inhibitory phosphates to activate the complex

3. Once active, the complex promotes mitiotic entry, and amplifies it’s own activation via positive feedback loop using CDC25

(this checkpoint ensures cell is redy for mitosis and DNA is replicated)

What is the purpose of the Metaphase to Anaphase Checkpoint?

• Explain the Process

Ensures all chromosomes are properly attached to the spindle MT’s via Kinetochores before segregation

• The mad and bub complex assemble at

List and Explain the 2 complexes the Restriction Point is regulated by.

• Explain the process on the Checkpoint

Cyclin D-CDK4/6: Initiates Phosphorylation of the retinoblastoma protein (RB)

Cyclin E-CDK2: further phosphorylates RB to sustain the process

1. RB binds and inhibits E2F TF’s preventing gene expression for S phases

2. Phosphorylation of RB → conformational change = releasing E2F

3. The E2F activates transcription of genes needed for DNA synthesis, including cyclin E (positive feedback loop)

4. Growth factor signaling through tyrosine kinase receptor activates RAS signaling cascade = promotes cyclin D expression and Cell cycle entry

5. Signaling Pathways like Pl3 kinase promote cell growth and survival