Cell Cycle 1

Why is the cell cycle important in multicellular organisms?

It allows development from a single fertilized egg through controlled cell growth and division at appropriate times and locations

What happens when cell division occurs at inappropriate times and places?

Tumor growth occurs

What two basic tasks must cells accomplish during the cell cycle?

• Copy cellular components

• Divide to distribute components evenly to daughter cells

What is the “cell cycle”?

The alternating “growth” and “division” activities of the cell

What are the “M phase” and “Interphase”?

• M phase: Cell division

• Interphase: Growth and preparation for division

What are common model systems used to study the cell cycle?

• Genetics: Yeasts — Schizosaccharomyces pombe (fission) and Saccharomyces cerevisiae (budding)

• Biochemistry: Sea urchin, starfish, and frog eggs

What are “periodic proteins”?

Proteins whose synthesis and degradation are cyclic during the cell cycle (e.g., cyclins), controlling enzyme activation and inactivation

What are the main phases of the cell cycle?

• G1

• S

• G2

• M (mitosis + cytokinesis)

What happens during G1 phase?

• Cell growth

• Preparation of chromosomes for replication

• Duplication of cellular components

• G1 checkpoint (restriction point): cell commits to division or exits cycle

What happens during S phase?

• DNA replication (all chromosomes duplicated)

• Duplication of the centrosome, which contains two centrioles that migrate to poles to form spindle poles

What happens during G2 phase?

• Further cell growth

• Checkpoint ensuring readiness for entry into M phase

What happens during M phase?

• Cell division (mitosis)

• Subdivided into six stages: Prophase, Prometaphase, Metaphase, Anaphase, Telophase, Cytokinesis

Describe Prophase events

• Chromosomes condense (require condensin and DNA topoisomerase II)

• Duplicated centrosomes separate

• Histones undergo mitosis-specific modifications

Describe Prometaphase events

• Microtubules attach to kinetochores

• Nuclear envelope breaks down

• Chromosomes start to align

Describe Metaphase events

• All chromosomes make bipolar attachments

• Align at metaphase plate

• Transition to anaphase is tightly regulated

Describe Anaphase events

• Chromatids separate and move toward opposite poles

• Poles separate further

• Nuclear envelope reassembly begins

Describe Telophase events

• Nuclear envelope reassembles

• Chromosome movement continues

• Cleavage plane specified

Describe Cytokinesis events

• Physical separation of daughter cells

• Cleavage furrow forms via actin contractile ring

• Chromosomes decondense and nuclear structures reform

What are kinases and phosphatases?

• Kinases: Enzymes that add phosphate groups to proteins

• Phosphatases: Enzymes that remove phosphate groups

What are cyclin-dependent kinases (CDKs)?

• Enzymes controlling cell cycle progression

• Have catalytic domains

• CDK levels remain constant

• Require cyclins for activation

What are cyclins?

• Proteins whose levels fluctuate through the cell cycle

• Primary regulators of CDKs

• Bind and activate CDKs to phosphorylate target proteins

List major Cyclin–CDK complexes by phase

• G1: Cyclin D–CDK4/6; Cyclin E–CDK2

• S: Cyclin E–CDK2; Cyclin A–CDK2

• G2: Cyclin A–CDK2; Cyclin A–CDK1

• M: Cyclin A–CDK1; Cyclin B–CDK1 (MPF – mitosis promoting factor)

How are CDKs activated?

• Cyclin binding

• Phosphorylation of activation loop by CDK activating kinases (CAKs)

How are CDKs inhibited?

• Inhibitory phosphorylation by Wee kinases (reversed by CDC25 phosphatases)

• Binding of CDK inhibitors (CDKIs): small tumor suppressor proteins

How is cyclin degraded?

Via ubiquitin-mediated degradation, ensuring periodic protein levels