Cell Cycle & Cell Division

Cell Cycle Overview

• The cell cycle and cell division are important processes
• Cell division in unicellular organisms results in reproduction by cell division
• Cell division in multicellular organisms supports asexual and sexual reproduction

Cell Division in Multicellular Organisms

• Development originates from a fertilized cell undergoing cell division throughout life
• Cell division contributes to organism growth and repair

Basis of Cell Division

• Eukaryotic cell genetic material resides within a nucleus
• Nucleus divides through mitosis and cytoplasm divides through cytokinesis
• DNA duplicates before being transferred to each daughter cell

Chromosomes

• Genome is the complete genetic information within an organism's chromosomes
• Chromosomes package DNA molecules
• Chromatin is a DNA-protein complex that condenses during cell division
• Each eukaryotic species possesses a characteristic number of chromosomes
• Humans have 46 chromosomes, fruit flies have 8, and king crabs have 208

Eukaryotic Chromosomes

• Diploid cells feature a complete set of chromosomes, always an even number
• Diploid cells comprise two sets of chromosomes, represented as 2n = 46, and includes somatic cells
• Haploid cells contain half a set of chromosomes
• Gametes are haploid, having one set of chromosomes, represented as n = 23
• DNA replicates and chromosomes condense in preparation for cell division

Duplicated Chromosomes

• Sister chromatids means 1 chromosome = 2 sister chromatids
• The centromere is the region where sister chromatids are closely attached

Cell Division

• Eukaryotic cell division for somatic cells includes mitosis and cytokinesis
• Mitosis is the division of genetic material in the nucleus
• Cytokinesis is the division of the cytoplasm
• Eukaryotic cell division for germ cells includes meiosis
• Meiosis produces gametes from germ cells
• Meiosis yields non-identical daughter cells, each with one set of chromosomes, half the parent cell's number

Cell Cycle Phases

• Interphase occupies 90% of the cell cycle including:
  • G1, the first gap where the cell grows and prepares for DNA replication
  • S, DNA synthesis where genetic material is duplicated
  • G2, the second gap, where the cell prepares for mitosis
• Mitotic phase (M Phase) lasts about 1 hour
  • Mitosis which has the phases prophase, metaphase, anaphase and telophase
  • Cytokinesis follows mitosis, completing cell division

Mitotic Spindle

• The mitotic spindle is an array of microtubules controlling chromosome movement during mitosis
• Spindle forms during prophase and prometaphase
• Spindles originate from the centrosomes in animal cells, that include centrioles, spindle microtubules, and asters
• Kinetochores have motor proteins associated with specific DNA sections at the centromere
• Each sister chromatid is connected to one kinetochore

Kinds of Microtubules in the Mitotic Spindle

• Kinetochore microtubules attach to chromosomes
  • They move chromosomes to the metaphase plate
• Non-kinetochore microtubules
  • They overlap and elongate the cell during anaphase

Key points of Anaphase

• In anaphase, sister chromatids separate and move along the kinetochore microtubules (via motor proteins) towards opposite ends of the cell

Cytokinesis of Animal Cells

• Cell divides into two
• Animal cells undergo cleavage
• A cleavage furrow forms
• A contractile ring forms inside, pinching the parent cell in two

Cytokinesis of Plant Cells

• Plant cells form a cell plate in the middle during telophase
• Vesicles from the Golgi apparatus move to the middle of the cell and fuse
• These carry cell wall material
• The cell plate enlarges, fusing with the plasma membrane
• Results in two daughter cells with a cell wall in between

Cell Cycle Regulation

• Cell division frequency varies with cell type
  • Some cells divide continually, such as skin cells
  • Liver cells can divide, but only if damaged
  • Mature nerve and muscle cells are unable to divide

Cell Cycle Regulation in Detail

• The cell cycle has sequential events regulated by a control system
• Molecules in the cell trigger and coordinate key events
• The cell cycle proceeds on its own using a built-in clock
• Cell Cycle regulated at checkpoints

Cell Cycle CheckPoints

• Checkpoints are control points where the cycle halts until a go-ahead signal is received
• Checkpoints respond to internal and external signals
• Signals transmit within the cell via transduction pathways

Kinds of Cell Cycle Checkpoints

• There are G1, G2, and M checkpoints
• The G1 phase checkpoint involves critical control
  • It may be called the restriction point
  • It issues a go or no-go signal
  • If no-go, the cell enters G0, a non-dividing state for most human cells (e.g., muscle, nerve, liver)
• The G2 checkpoint happens at prometaphase
  • During mitosis, cells get a stop signal if chromosomes aren't attached to spindle fibers
• The M checkpoint:
  • At Metaphase, attachments to spindle fibers from both poles trigger a go-ahead signal, allowing the cell to proceed into anaphase
  • This happens when all chromosomes attach correctly

Cell Cycle Regulation on a Molecular Level

• Abundance and activity of regulatory molecules are important
• There are two regulatory poteins:

1. Cyclins - which fluctuates
2. Cyclin-dependent kinases (Cdks)
   • These enzymes activate/inactivate other proteins by phosphorylating them
   • They drive the go-ahead signals at G1 and G2 checkpoints
   • Activity fluctuates due to cyclin concentration control

Types of Regulatory Proteins

• MPF (maturation-promoting factor) = cyclin-Cdk complex
  • It triggers a cell's passage past the G2 checkpoint into the M phase
  • MPF is self-regulating by degrading its cyclins in anaphase

Internal Signals

• The M phase checkpoint
  • Is also called APC (anaphase-promoting complex)
  • It controls the start of anaphase
  • But only works if all kinetochores are attached to kinetochore microtubules
  • Thus daughter cells lack missing or extra chromosomes

External Signals

• Need chemical and physical external signals
• External growth factors (mammalian cells): >50 g.f.
  • Proteins are released by one cell, to stimulate another cell's division
    • E.g., PDGF (platelet-derived growth factor)
    • Released near injured tissue so fibroblasts can pass G1 and divide to heal the wound
• density-dependent inhibition:
  • Crowded cells stop dividing
  • When cells touch, growth inhibiting signals stop the cell cycle
• anchorage dependence:
  • Cells must be attached to a substratum for it to divide

Cancer Cells

• Cancer cells have a loss of cell cycle controls
• Cancer cells tend to fail density-dependent inhibition or anchorage dependence
• Cancer cells do not respond normally to the body’s control mechanisms
• Cancer cells divide excessively if there are nutrients
• Cancer cells lack growth factor and do not stop division
• Cancer cells form tumors:
  • Benign tumors stay at the origin and can be removed without harm
  • Malignant tumors invade tissues, impacting function that requires radiation
  • Metastasis: tumor cells export and spread via blood or lymph and require Chemotherapy