The Cell CycleCONSISTING OF INTERPHASE ,MITOTIC PHASE, &

CYTOKINESIS

The Mitosis Puzzle

Lay blank sheet lengthwise .

Write Interphase, Prophase, Metaphase, Anaphase, & Telophase across the top of the sheet.

Cut out the cell diagrams and tape/glue them across the top under the appropriate phase label.

Arrange each description beneath the appropriate picture to describe the cellular changes of that phase.

Why do cells divide?• Bacteria cells & unicellular eukaryotic

organisms divide & produce an entire organism.

• Multi-cellular organisms: – Development -Growth -Repair

What do you get at the end of the cell cycle?

2 genetically identical daughter cells

Cellular Organization

PROKARYOTIC EUKARYOTIC

Approximately 2 m of DNA to

copy & be separated

Replication of so much DNA is manageable because of how DNA is packaged.

chromosomes

chromatin

Does the number of chromosomes in an organism determine how complex the

organism is?

Bat

Herring gull

Human

Crayfish

Fern

Reptiles

Dog

Organize the following organisms in order from complex to simple

Parts of a chromosome

THIS CHROMOSOME IS A DUPLICATED CHROMOSOME WITH 4 CHROMOSOMAL ARMS

The Cell Cycle• Interphase – Accounts for 90% of the cycle– Divided up into 3 subunits

The Cell Cycle• Mitotic phase– Includes both mitosis and cytokinesis– Usually the shortest part of the cell cycle.

and Cytokinesis

Mitotic Spindle• Begins to form during prophase & is complete during

metaphase

Starts here

Form from the breakdown of microtubules of the cytoskeleton

Not present in plant cells

What is the significance of the fact that chromosomes condense before they are moved?

WHICH OF THESE WOULD YOU RATHER ORGANIZE WITHOUT BREAKING?

CYTOKINESISANIMAL CELLS PLANT CELLS

BINARY FISSION

PROKARYOTES (BACTERIA & ARCHEA)

Evolution of Mitosis

A protein is thought to anchor the DNA to specific spot on membrane

Timing is everything!• The frequency of cell division varies with cell

type.– EX: human skin cells vs liver cells

• Some cells do not divide at all in a mature human.– EX: nerve cells and muscle cells

What was concluded?

Molecules present in the cytoplasm of cells in the S

or M phase control the progression of phases.

What Drives The Cell Cycle?

Hypothesis: -Each event in the cycle triggers the next.

CELL CYCLE CONTROL SYSTEM

THE G1 CHECKPOINT

The Cell Cycle Clock

• Maturation/Mitosis Promoting Factor (MPF) are regulatory molecules (mainly proteins)–Protein kinases and cyclins plus a

phosphate group

•Kinases are enzymes• Activate or inactivate other proteins by

phosphorylating them.•Give the go ahead signals at the G1 and G2

checkpoints.• Present in a constant concentration in a growing

cell, but are mostly inactive.• To be active they must attach to a cyclin (a

protein) = cyclin-dependent kinases, or Cdks

Cyclin and Kinases

Cyclin D triggers cells to move from G0 to G1 into S phaseCyclin E prepares the cell for DNA replication in S phaseCyclin A activates DNA replication inside the nucleus in S phaseCyclin B promotes the assembly of the mitotic spindle & other tasks in the cytoplasm to prepare for mitosis

Cyclins and cyclin-dependent kinases control the cell cycle.

After the MPF does its job the cyclin degrades. Why?

The cell would continue to divide even when not ready

In summary

• Internally:– The fluctuation of cyclin & cyclin-dependent

kinases seems to control the cell cycle internally using checkpoints to tell the cell to proceed or not

– The MPF complexes (cyclin + Cdk) initiates mitosis & can then go on to produce a cascade of other cell responses including phosphorylation of other proteins which:• Promotes fragmentation of nuclear envelope• Chromosome condensation and spindle formation

What about external factors?

Example of a growth factor is PDGF (platelet-derived growth factor)

PDGF is required for the division of fibroblasts (a type of connective tissue)

Triggers a transduction pathway allowing the cells to pass the G1 checkpoint & divide.

An injury can instigate this growth factor to help heal a wound.

MORE EXTERNAL FACTORS ON CELL DIVISION:

DENSITY-DEPENDENT INHIBITION (in culture)

In summary

• Externally:– Growth factors secreted from the endocrine

glands or blood cells are present– A substrate to attach to is needed– Density of neighboring cells are a factor– Receptors (on outside of cell that’s dividing) are

needed to receive each of the cell signals mentioned above.

When do cells fail to divide?If essential nutrients are missing.

If growth factors ( protein released by certain cells to stimulate other cells to divide) are missing.

Note: there are more than 50 growth factors

Let’s look at a cell gone wrong in the video Non disjunction or non segregation in Mitosis

How does a cell divide “wrong”?

What is the definition of cancer?

• The unregulated cell division of an organism’s cell

LOSS OF CELL CYCLE CONTROLS

Cancer cells do not follow the normal signals that regulate the cell cycle.• They don’t stop dividing even when there are no growth factors present.• Can continue dividing indefinitely in culture with ample nutrients.

• EX: HeLa cells of 1951

MALIGNANT VS BENIGN TUMOR

What does it mean if the cancer has metastasized?

Have too few genetic & cellular changes to survive elsewhere.

Have genetic & cellular changes that enable the cells to spread to new tissues & impair functions of organs = cancer

Cancer most often results from mutations in genes

• Proto-oncogenes: they often code for proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis).

• Tumor suppressor genes- produce proteins that signal cells when they are getting too crowded.

How does someone “get cancer”?• It can be triggered by:– Carcinogens- Substances and environmental exposures that

can lead to cancer • Teratogens-Any agent that can disturb the development of an embryo

or fetus. Teratogens may cause a birth defect in the child. Or a teratogen may halt the pregnancy outright. The classes of teratogens include radiation, maternal infections, chemicals, and drugs.

– Viruses: ex: HPV (human papilloma virus) causes cervical cancer & EBV (Epstein Barr virus) is associated with Hodgkin’s lymphoma, and gastric cancer.

– Aging: ex: breast cancer increases the older you get

How can we kill cancer cells?

• Radiation• Chemotherapy– CDKs are considered a potential target for anti-

cancer medication. – If it is possible to selectively interrupt the cell cycle

regulation in cancer cells by interfering with CDK action, the cell will die.

– Targets fast dividing cells

Differentiation of Human Cells

A zygote starts development by dividing over and over until you get a few dozen

identical cells. These cells are embryonic stem cells.

What are stem cells?

Embryonic Stem Cells• Cells that start to take different development paths to become

specialized cells, such as blood stem cells, which means they can no longer produce any other type of cell.

Can give rise to any and all tissues in the body

they can differentiate into some, but not all, cell types.

Totipotent cells can form all the cell types in a body, plus the extra-embryonic, or placental cells.

Embryonic cells within the first couple of cell divisions after fertilization are the only cells that are totipotent.

Pluripotent cells can give rise to all of the cell types that make up the body; embryonic stem cells are considered pluripotent.

Multipotent cells can develop into more than one cell type, but are more limited than pluripotent cells; adult stem cells and cord blood stem cells are considered multipotent

TOTIPOTENT VS PLURIPOTENT VS MULTIPOTENT

Stem Cells Video

To generate cultures of specific types of differentiated cells—heart muscle cells, blood cells, or nerve cells, for example—scientists try to control the differentiation of embryonic stem cells. They change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes.

What side of stem cell research do you fall?