Mitosis (division of a nucleus)

• All of the DNA in a cell constitutes the cell’s genome

• Prior to cell division DNA molecules in a cell are packaged into chromosomes

• Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein

• Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus

• Somatic cells (non-reproductive cells): have two sets of chromosomes (2N)

• Gametes (reproductive cells: sperm and eggs): have one set of chromosomes (1N)

• Each duplicated chromosome has two sister chromatids, joined identical copies of the original chromosome

• The centromere is where the two chromatids are most closely attached.

• The cell cycle consists of

  • Mitotic (M) phase: including mitosis and cytokinesis

  • Interphase: includes cell growth and copying of chromosomes in preparation for cell division

• Eukaryotic cell division consists of

  • Mitosis: the division of the genetic material in the nucleus

  • Cytokinesis: the division of the cytoplasm and membrane

• Interphase (about 90% of the cell cycle) can be divided into subphases

  • G1 phase (“first gap”) - Cell growth organelle development

  • S phase (“synthesis”) - DNA is replicated

  • G2 phase (“second gap”) - preparation for division, DNA checked for errors

  • G0 - Cellular state outside of the replicative cell cycle (cell that does not divide again)

Cell Cycle Control

• Mitosis is divided into five phases (sometimes four)

  • Prophase

  • Prometaphase (sometimes left out)

  • Metaphase

  • Anaphase

  • Telophase

• The mitotic spindle is a structure made of microtubules and associated proteins

  • it controls chromosome movement during mitosis

• In animal cells, spindle microtubules begin to form at the centrosome, a type of microtubule organizing center

• An aster (radial array of short microtubules) extends from each centrosome

• Kinetochores are protein complexes that assemble on sections of DNA at centromeres.

• In anaphase, sister chromatids separate and move along the kinetochore microtubules towards opposite ends of the cell

• The microtubules shorten by depolymerizing at their kinetochore ends

  • depolymerizing: losing amino acids at the ends of the proteins

• Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission

• The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a timing device of a washing machine

• The cell cycle control system is regulated by both internal and external controls

• The system has specific checkpoints where the cell cycle stops until a go-ahead signal is received

• The cell cycle is regulated by a set of regulatory proteins including kinases and proteins called cyclins

• Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide

• Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing

• Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide.

Cell Cycle Checkpoints

Checkpoint #1

• For many cells, the G1 checkpoint seems to be the most important

• The G1 checkpoint sends a “go-ahead” signal for the cell to initiate the process, when given a cell will usually complete the S, G2, and M phases and divide

• If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

Checkpoint #2

• The G2 phase checkpoint occurs prior to mitosis

• The G2 checkpoint ensures all of the chromosomes have been replicated and that the replicated DNA is not damaged before the cell enters mitosis

Checkpoint #3

• The M phase checkpoint occurs during mitosis

• This checkpoint ensures kinetochores (chromosomes) are attached to the spindles

• Attachment of all of the kinetochores activates a regulatory complex, which then activates the enzyme separase allowing the chromosomes to separate

• Separase allows sister chromatids to separate, triggering the onset of anaphase, without it anaphase does not happen.

Cell Cycle Control and Cancer

• Tumor cells do not respond to signals that normally regulate the cell cycle

• Cancer cells do not need growth factors to grow and divide

  • They may make their own growth factor

  • They may convey a growth factor signal without the presence of the growth factor

  • They may have an abnormal cell cycle control system

• a normal cell is converted to a cancerous cell by a process called transformation

• cancer cells are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue

• if abnormal cells remain only at the original site, the lump is called a benign tumor

• Malignant tumors invade surrounding tissues and undergo metastasis, exporting cancer cells to other parts of the body, where they may form additional tumors

• p53 gene - a tumor suppressor gene. When functioning properly it prevents the development of tumor

• Oncogene - a mutated gene that has the potential to cause cancer. Before an oncogene becomes mutated, it is called a proto-oncogene, and it plays a role in regulating normal cell division

• Apoptosis - programmed cell death. This occurs in three parts

  • Chromatin condensation

  • Membrane blebbing (nucleus condensing)

  • apoptotic body formation

• How does cancer kill?

  • Absorbs nutrients needed by other cells

  • blocks nerve connections

  • prevents organs from functioning properly

Cell Signaling

• Autocrine signaling: signals created and sent by a cell that are later received by receptors in the same cell (sender and target cell are the same).

  • these signals are often triggered by external stimuli

  • often never leaves the cell membrane

    • cyclins - used at mitosis checkpoints

    • growth hormones made by cancer cells for cancer cells

• Juxtacrine signaling: Cells have direct connections to nearby cells: These are called gap junctions (animal cells) and plasmodesmata (plant cells)

  • touching cells only

• Paracrine signaling: the type of local signaling in animal cells

  • These messenger molecules, called local regulators, travel only short distances

  • happens most commonly in animal cells - can happen in plants tho

  • eg. growth factors - used in healing

• Synaptic signaling (paracrine) consists of an electrical signal moving along a nerve cell that triggers secretion of neurotransmitter molecules

  • These diffuse across the space between the nerve cell and its target, triggering a response in the target cell

  • animal nervous system only

Cell signaling reception and response

• the hydrophobic signaling molecules require a carrier protein to travel through the extracellular matrix, but can diffuse freely across the cell membrane. Ex. Steroids (lipids, inorganic molecules)

• Most signaling molecules are hydrophilic, so they don’t require a carrier protein, but need a membrane-bound receptor protein to enter the target cell.

• There are three main types of membrane receptors

  • G protein-coupled receptors*

  • Enzyme-coupled receptors*

    • Enzyme-coupled receptors: the binding of an extracellular ligand causes enzymatic activity on the intracellular side.

  • Ligand-gated ion channels

    • Ligand-gated ion channel receptor acts as a “gate” for ions when the receptor changes shape

    • Ligand-gated ion channels are very important in the nervous system (synaptic signaling

    • The diffusion of ions through open channels may trigger an electric signal

• * more complicated requires further steps

• Cells receiving signals undergo three processes

  1. Reception (at membrane)

     • The binding of a signaling molecule to a receptor protein

       • the binding between a signal molecule (ligand) and receptor is highly specific

       • ligand binding generally causes a shape change in the receptor

       • many receptors are directly activated by this shape change as most receptors are membrane proteins.

  2. Transduction (cytoplasm)

     • Transduction by cascades of molecular interacts

       • Signal transduction (step two) usually involves multiple steps

       • Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

       • A signaling pathway involving phosphorylation and dephosphorylation can be referred to as a phosphorylation cascade

  3. Response (nucleus)

     • Regulation of transcription or cytoplasmic activities

       • Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities

       • The response may occur in the cytoplasm or in the nucleus

       • Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus

       • The final activated molecule in the signaling pathway may function as a transcription factor

• Intracellular receptor proteins are found in the cytosol or nucleus of target cells for hydrophobic ligands

• small or hydrophobic chemical messengers can readily cross the membrane and activate receptors

• examples of hydrophobic messengers are the steroid and thyroid hormones of animals and nitric oxide (NO) in both plants and animals

• Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion

  • Cyclic AMP (cAMP) is one of the most widely used second messengers

  • Adenylyl cyclase, an enzyme in the plasma membrane, rapidly converts ATP to cAMP in response to a number of extracellular signals

• Homeostasis - the state of steady internal, physical, and chemical conditions maintained by living systems.*

• *this is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance

• Negative feedback: negative feedback loops allow systems to self-stabilize by reducing or dampening the process that pushed the organism out of balance.

• Positive feedback loop: moves a system further away from the target of equilibrium. It does this by amplifying the effects of a product or event and occurs when something needs to happen quickly

  • ex. contractions during birth, ripening of fruit, fevers