Cell Cycle & Homeostasis Feedback

  • The cell division process is an integral part of life

    • Allows for the reproduction of cells, growth of cells, and tissue repair

  • Cell cycle: the life of a cell from its formation until it divides

Organization of DNA

Cells must organize and package their DNA before division

  • DNA associates with and wraps around proteins known as histones to form nucleosomes

    • Strings of nucleosomes form chromatin

      • When a cell is not actively dividing, chromatin is in a non-condensed form

      • After DNA replication, chromatin condenses to form a chromosome

        • Chromosomes are densely packed to allow for easier division 

Since the DNA was replicated, each chromosome has a duplicated copy

  • The copies join together to form sister chromatids 

    • Centromere: the region on each sister chromatid where they are most closely attached 

    • Kinetochore: proteins attached to the centromere that link each sister chromatid to the mitotic spindle

Genome

Genome: all of a cell’s genetic information (DNA)

  • Prokaryotes: singular, circular DNA

  • Eukaryotes: one or more linear chromosomes

    • Every eukaryote has a specific number of chromosomes

      • Humans: 46

      • Chimps: 48 

      • Elephants: 56

  • Homologous chromosomes: two chromosomes (one from mom and one from dad) that are the same length, have the same centromere position, and carry genes controlling the same characteristics

Types of Cells

Somatic Cells: Body cells

  • Diploid (2n): two sets of chromosomes, one set from each parent

  • Divide by mitosis

  • Humans: 2n=46

    • 23 from mom

    • 23 from dad

Gametes: Reproductive cells (eggs/sperm)

  • Haploid (n): one set of chromosomes

  • Divide by meiosis

  • Humans: n=23

Cell Cycle

  • The cell cycle consists of alternating phases of interphase and mitosis

    • G1→ S→ G2 → mitosis → cytokinesis

Interphase

Interphase

  • The longest portion of the cell cycle (90%)

    • G1 “first gap” phase

      • The cell grows and carries out normal functions

    • S “synthesis” phase

      • DNA replication and chromosome duplication occurs

    • G2 “second gap” phase

      • Final growth and preparation for mitosis

M Phase

  • Mitosis: nucleus divides

  • Cytokinesis: cytoplasm divides

  • Mitosis results in 2 identical diploid daughter cells

Phases of Mitosis

Mitosis is broken down into 5 stages:

  1. Prophase

  2. Prometaphase

  3. Metaphase

  4. Anaphase

  5. Telophase and cytokinesis

Prophase:

Key events:

  • Chromatin condenses

  • Nucleoli disappear

  • Duplicated chromosomes appear as sister chromatids

  • Mitotic spindle begins to form

  • Centrosomes move away from each other

Prometaphase:

Key events:

  • Nuclear envelope fragments

  • Microtubules enter nuclear area and some attach to kinetochores

Metaphase:

Key events:

  • Centrosomes are at opposite poles

  • Chromosomes line up at the metaphase plate

  • Microtubules are attached to each kinetochore

Anaphase:

Key events:

  • Sister chromatids separate and move to opposite ends of the cell due to the microtubules shortening

  • Cell elongates

Telophase:

Key events:

  • Two daughter nuclei form

  • Nucleoli reappear

  • Chromosomes become less condensed

Cytokinesis:

  • Animals: a cleavage furrow appears due to a contractile ring of actin filaments

  • Plants: vesicles produced by the Golgi travel to the middle of the cell and form a cell plate

Binary Fission

  • Mitosis in eukaryotes likely evolved from binary fission in bacteria

    • single circular chromosome

    • no membrane-bound organelles

  • A possible progression of mechanisms intermediate between binary fission & mitosis seen in modern organisms

Regulation of the Cell Cycle

  • Throughout the cell cycle there are checkpoints

    • Control points that regulate the cell cycle

      • Cells receive stop/go signals

Major Checkpoints

G1 Checkpoint - can DNA synthesis begin?

  • Most important checkpoint

  • Checks for cell size, growth 

factors, and DNA damage

  • “Go”- cell completes 

the whole cell cycle

  • “Stop”- cell enters a 

nondividing (quiescent) 

state known as G0 phase

G0

  • Non dividing stage

  • Some cells stay in G0 forever (muscle/nerve cells)

  • Some cells can be called back into the cell cycle (liver cells)

G2 Checkpoint

  • Checks for completion of DNA replication and DNA damage

  • “Go”--cell proceeds to mitosis

  • “Stop”-- cell cycle stops and the cell will attempt to repair damage

    • If damage cannot be repaired the cell will undergo apoptosis

      • Programmed cell death

M (Spindle) Checkpoint

  • Checks for microtubule attachment to chromosomes at the kinetochores at metaphase

  • “Go”--cell proceeds to anaphase and completes mitosis

  • “Stop”-- cell will pause mitosis to allow for spindles to finish attaching to chromosomes

Internal Cell Cycle Regulators

  • cell cycle internal control system:

  1. Cyclins (proteins)

    • Concentration of cyclins varies 

      • Cyclins are synthesized and degraded at specific stages of the cell cycle

  2. cyclin-dependent kinases (CDKs) [enzymes]

    • Concentration remains constant through each phase of the cell cycle

      • Active only when its specific cyclin is present

    • Phosphorylates cellular proteins

  • Each cyclin-CDK complex has a specific regulatory effect

    • Active CDK complexes phosphorylate target proteins, which help regulate key events in the cell cycle

External Cell Cycle Regulators

  • Growth factors: hormones released by cells that stimulate cell growth

    • Signal transduction pathway is initiated 

      • CDKs are activated leading to progression through the cell cycle

  • Contact (or density) inhibition: Cell surface receptors recognize contact with other cells

    • Initiates signal transduction pathway that stops the cell cycle in G1 phase

  • Anchorage dependence: cells rely on attachment to other cells or the extracellular matrix to divide

Cancer: Evasion of the Cell Cycle

  • Normal cells become cancerous through DNA mutations (ex in proto-oncogenes or tumor-suppressor genes)

    • DNA mutations: changes in the DNA

      • Cancer cells on average have accumulated 60 or more mutations on genes that regulate cell growth

Normal Cells:

  • Follow checkpoints 

  • Divide on average 20-50 times in culture (in petri dishes)

  • Go through apoptosis when there are significant errors

Cancer Cells:

  • Do not follow checkpoints

  • Divide infinitely when in culture

    • Considered to be “immortal”

  • Evade apoptosis and continue dividing even with errors 

Cancer Cells

  • The uncontrollable growth of cancer cells can lead to a tumor

    • A mass of tissue formed by abnormal cells

      • Benign tumor: cells are abnormal, but not considered to be cancerous (yet)

        • Cells remain at only the tumor site and are unable to spread elsewhere in the body

      • Malignant tumor: mass of cancerous cells that lose their anchorage dependency and can leave the tumor site

        • Metastasis: when cells separate from the tumor and spread elsewhere in the body

Homeostasis and Feedback

The body must be able to monitor its internal conditions at all times

  • Set points: values for various physiological conditions that the body tries to maintain

    • This set point has a normal range for which it can fluctuate

      • Example: body temperature

        • Set point: 98.6℉

        • Normal range: 97℉ to 99℉

Homeostasis: the state of relatively stable internal conditions

  • Organisms detect and respond to a stimulus

  • Think: balance

The body maintains homeostasis through feedback loops

Feedback Loops:

There are two types of feedback loops: negative and positive

Terms to know:

Stimulus: a variable that will cause a response

Receptor/sensor: sensory organs that detect a stimulus. This information is sent to the control center (brain)

Effector: muscle or gland that will respond

Response: changes (decreases or increases) the effect of the stimulus 

Negative Feedback:

  • The most common feedback mechanism

  • This type of feedback reduces the effect of the stimulus

    • Examples:

      • Sweat

      • Blood sugar

      • Breathing rate

Positive Feedback:

  • This type of feedback increases the effect of a stimulus

    • Examples:

      • Child labor

      • Blood clotting

      • Fruit ripening

Homeostatic Imbalances

There are many reasons for why the body may not be able to regulate homeostasis

  • For example:

    • Genetic disorders

    • Drug or alcohol abuse

    • Intolerable conditions (ie extreme heat or cold)

Disease: when the body is unable to maintain homeostasis

  • Examples:

    • Cancer: the body cannot regulate cell growth

Diabetes: the body cannot regulate blood glucose levels

Cell Signaling as a Means of Homeostasis

  • In order to maintain homeostasis, the cells in a multicellular organism must be able to communicate

  • Communication occurs through signal transduction pathways