Review What is the purpose of mitosis? What is the cell cycle? What are the phases of mitosis? Describe at least one event from each phase.

Chapter 12: The Cell Cycle Rudolf Virchow-1855 “Omnis cellula e cellula” Every cell from a cell. Cells reproduce to form genetically equivalent daughter cells.

Roles of Cell Division Reproduction Growth Repair In all cases, cell division must distribute identical genetic material to two daughter cells.

Genome The cell's hereditary endowment of DNA. Usually packaged into chromosomes for manageability. Chromosomes Made of a DNA and protein complex called Chromatin. During cell division, the chromatin becomes highly condensed into the chromosomes.

Chromosomes - Structure At cell division, each chromosome has been duplicated. The duplicated chromosome consists of two sister chromatids.

Cell Cycle - parts 1. Interphase - (90% of cycle) - when the cell grows and duplicates the chromosomes. 2. Mitotic Phase (M) - when the chromosomes are split into separate cells.  Mitosis – equal division of replicated chromosomes, by separation of the sister chromatids into separate cells.  Cytokinesis - division of the cell’s cytoplasm.

Cell grows and carries out regular biochemical functions. When the DNA is replicated or synthesized. Cell completes preparations for division. Centrosomes and organelles are replicated.

Interphase Centrosome, made of two centrioles is replicated.

Mitosis Steps Prophase Prometaphase Metaphase Anaphase Telophase

Prophase

1. Nucleoli disappear. 2. Chromatin condenses into the chromosomes. 3. Centrosomes separate to opposite ends of the cell. 4. Mitotic spindle begins to form.

Prophase

Prometaphase

1. Nuclear envelope dissolves. 2. Spindle fibers attach to the kinetochore (a structure of proteins and specific sections of chromosomal DNA) of the centromeres.

Prometaphase

Metaphase - movie

Metaphase 1. Centrosomes now at opposite ends of the cell. 2. Chromosomes line up on the metaphase plate. 3. Spindle apparatus fully developed.

Metaphase

Anaphase

1. Centromeres break and the duplicate chromosomes are pulled away from each other toward opposite ends of the cell. Kinetochore appear to “ratchet” the chromosome down the spindle fiber microtubule with a motor protein. Microtubules dissolve behind the kinetochore (shown with laser microbeam wxperiment) 2. Cell elongates; poles move slightly further apart.

Microtubules shorten only on the kinetochore side.

Anaphase

Telophase

1. Chromosomes uncoil back to chromatin. 2. Nuclear envelope reforms. 3. Nucleoli reappear. 4. Spindle fibers disappear. 5. Cytokinesis usually starts.

Telophase

Cyotkinesis

Cytokinesis

Animal Cleavage furrow forms. Microfilaments contracts and divides the cytoplasm into two parts. Plants Cell plate develops from Golgi vesicles. New cell wall developed around the cell plate.

Cell Plate

Cell Division

Animal Cell - Mitosis

Plant Cell - Mitosis

Evolution of Mitosis

Regulation of Cell Division Must be controlled. Rate of cell division depends on the cell type. Ex - skin: frequently liver - as needed brain - rarely or never

Checkpoints A critical control point in the cell cycle. Several are known. Cells must receive a “go-ahead” signal before proceeding to the next phase. G 1 Checkpoint Also called the “restriction point” in mammalian cells. Places cells in a non-dividing phase called the G o phase.

G o Phase Non-dividing state. Most cells are in this state. Some cells can be reactivated back into M phase from the G o phase.

Protein Kinase Checkpoint - G 2 Uses protein kinases to signal “go-ahead” for the G 2 phase. Activated by a protein complex whose concentration changes over the cell cycle. M-phase Promoting Factor (MPF). Protein complex required for a cell to progress from G 2 to Mitosis. Role of MPF - to trigger a chain of protein kinase activations.

Active M-phase Promoting Factor (MPF) has: 1. Cdk (Cyclin dependent kinase) is a Protein Kinases (activates and deactivates other proteins by phosphoryalating them. Amount remains constant during cycle. Inactive unless bound with cyclin. When enough cyclin is present, active MPF is formed. 2. Cyclin Protein whose concentration builds up over G 1, S and G 2, then falls abruptly during Mitosis.. The activity of Cdk rises and falls with changes in the concentration of its cyclin partner.

Active M-phase Promoting Factor (MPF) Triggers Mitosis. Activates a cyclin-degrading enzyme, which lowers the amount of cyclin in the cell. Result - no active MPF to trigger another mitosis until the cycle is repeated.

Growth Factors External signals that affect mitosis. Examples: 1. Platelet-Derived Growth Factor (PDGF) Stimulates cell division to heal injuries. 2. Density-dependent inhibition The number of cells in an area force competition for nutrients, space, and growth factors.  When density is high - no cell division.  When density is low - cells divide. 3. Anchorage dependence

PDGF

Density-Dependent Inhibition

Growth Factors (Continued) External signals that affect mitosis. Examples: 3. Anchorage dependence Inhibition of cell division unless the cell is attached to a substratum. Prevents cells from dividing and floating off in the body.

Cancer Cells Do not stop dividing. The control mechanisms for cell division have failed.

Comment Regulation of cell division is a balance between: Mitosis - making new cells. Apoptosis - cell suicide. Cancer can result if either process doesn’t work.

Summary Know the phases and steps of the cell cycle. Be able to discuss the “regulation” of the cell cycle. Cell cycle animation mitosis tutorial onion cell mitosis activity mitosis tutorial (U of Arizona) animal cell mitosis