Cell Cycle and Mitosis Notes

Cell Cycle

Overview

• The cell cycle is how two cells become one.
• Two phases:
  • Mitosis: Active cell division.
  • Interphase: Time when cell grows and prepares for cell division.

Interphase

• Subdivided into G1, S phase, and G2.
• G1 Phase:
  • Cell is "chilling", carrying out normal metabolic functions, and growing.
• S Phase:
  • DNA replication occurs.
• G2 Phase:
  • Cell readies for mitosis, and continues to grow.

Cell Cycle Schematic

• M phase: Active cell division.
• Interphase: G1, S, and G2 phases.
• G1: Normal metabolic function and growth.
• S phase: DNA synthesis/replication.
• G2: Getting ready for mitosis and more growth.

G0 Phase

• When a cell enters G0, it is not dividing or thinking about dividing.
• Examples: Muscle cells and neurons.
• These cells have "left the cell cycle", typically from G1.

Why Divide?

• To produce reproductive cells (gametes).
• For organism growth.
• To repair.
• To maintain tissue.

How: Organizing a Signal

• A signal tells the cell it's time to divide.
• Examples:
  • Growth factors.
  • Interleukins (IL).
  • Erythropoietin.
  • Hormones (e.g., estrogen).
• The signal stimulates movement from G1 into S phase.
• S phase: Duplication of DNA.
• G2: Getting ready for mitosis.
  • Duplicating organelles.
  • Duplicating centrosomes.
  • Producing microtubules for the mitotic spindle.
• M phase: Active cell division.

M Phase (Mitosis) - Detailed

• PPMAT: Prophase, Prometaphase, Metaphase, Anaphase, Telophase, and Cytokinesis

Prophase

• Chromosomes condense.
• Genetic information is packed into chromosomes.

Chromosome Composition

• Chromosomes are made up of chromatin.
• Chromatin is comprised of DNA and proteins.
• DNA and proteins make up nucleosomes (beads on a string).
• Nucleosomes are made of DNA and histones.
• Histones:
  • H1 (linker histone).
  • H2A, H2B, H3, and H4 (core histones).

Nucleosome Structure

• Core histones: Two of each (H2A, H2B, H3, H4) = 8 total.
• DNA wrapped around core histones: 146 base pairs.
• H1 linker histone connects everything together.

Chromatin Compaction

• Multiple nucleosomes compact further.
• H1 histones link together to form a solenoid.
• Solenoid compacts into a 300 nm structure.
• Further compaction into loop structures.
• Final structure: Duplicated chromosome (after S phase).

Chromatin, Sister Chromatids, and Duplicated Chromosomes

• Chromatin: Tightly wound DNA and proteins.
• Sister chromatid: Each arm of the duplicated chromosome.
• Two sister chromatids make up the duplicated chromosome.

Centromere and Kinetochore

• Centromere: Area linking two sister chromatids together.
• Kinetochore: Area on the centromere where mitotic spindle fibers attach.

Mitotic Spindle Formation

• Mitotic spindle is made of microtubules.
• Microtubules come from the centriole.
• Centrioles originate from the centrosome (home of the centriole).

Nucleolus Disappearance

• Nucleolus disappears during prophase.
• The nucleolus is the area in the nucleus where ribosomes are assembled.
• Because chromosomes are condensed, transcription and translation are not occurring, so ribosomes are not needed.

Prometaphase

• Nuclear envelope/membrane breaks down and disappears.
• Mitotic spindle is fully formed and starts to attach to chromosomes, not fully attached.
• Kinetochore microtubules attach to kinetochores on the centromeres.

Metaphase

• Chromosomes line up in the middle of the cell on the equatorial plate.

Anaphase

• Separated chromosomes (sister chromatids) move to opposite ends/poles of the cell.

Telophase

• Nuclear membrane reforms (disappeared in prometaphase).
• Chromosomes have moved to opposite ends.

Cytokinesis

• Division of the cytoplasm.
• Two cells become one.
• Uses contractile microfilaments called actin and myosin.
• Contractile ring forms in the center and pinches the cell in two.

Additional Important Vocabulary

Euchromatin vs. Heterochromatin

• Euchromatin:
  • Active form.
  • Replicating, transcribing, translating.
  • Not wrapped around nucleosomes, so it is available.
• Heterochromatin:
  • Inactive form.
  • Wrapped around nucleosomes.

Histone Protein Modifications

• Can change heterochromatin to euchromatin, and vice versa, via histone protein modifications.

Acetylation

• Addition of a two-carbon molecule (acetyl group) to histones.
• Use HATs (histone acetyltransferases) to add an acetyl group to heterochromatin.
• HATs loosen the DNA-histone interaction, increasing transcription.
• Heterochromatin to euchromatin.

Deacetylation

• Removal of an acetyl group from euchromatin.
• Use HDACs (histone deacetylases) to remove the acetyl group.
• HDACs tighten the DNA-histone interaction, decreasing transcription.
• Euchromatin to heterochromatin.

Chromosomal Mutations

• See lecture 13 video for more details.