The Cell Cycle

The Cell Cycle

Biological Science, Chapter 11

April 18/23, 2012

Learning Outcomes

• After the study of this chapter and lecture notes, you should be able to…–discuss the need for asexual

reproduction,

–describe the stages of the cell cycle,

–describe the manifestation of cancer, and

–discuss the importance of control over the cell cycle.

i>clicker Survey: Agree (A) or Disagree (B)

• When a cell divides, two cells are formed.

• The lifetime of all cells is about the same.

• A single double helix of DNA composes a chromosome.

• Cells can undergo cellular suicide.

• DNA must be condensed for mitosis to occur.

• All cancers are due to a single mutated gene.

11.1 Mitosis and the Cell Cycle

• Asexual reproduction results in offspring that are genetically identical to the parent.

• Cell division in unicellular organisms (like prokaryotes) occurs through asexual reproduction.

Asexual Reproduction in Prokaryotes

• The prokaryotic chromosome is organized differently than eukaryotic chromosomes.

• The bacterial chromosome is a circular loop.

Asexual Reproduction in Prokaryotes

• Binary fission produces two (binary) identical daughter cells from a parent cell.

• The cell enlarges, the chromosome replicates, and a new plasma membrane and cell wall appear.

In-Class i>clicker Question

• Which is the process that describes how prokaryotic cells divide?

A. meiosis

B. mitosis

C. binary fission

D. nuclear fission

E. cytokinesis


• The cell cycle takes place in eukaryotic cells.

• The cell cycle is a repeating sequence of growth, replication of DNA, and cell division.

• Two identical daughter cells are produced.


• Cells divide to produce identical daughter cells for three reasons:

– growth

– wound repair

– asexual reproduction


• The duration of cell cycle varies between types of eukaryotic cells.

Cell Type Cell-Cycle Times

frog embryo cells 30 minutes

yeast cells 1.5-3 hours

intestinal epithelial cells

~12 hours

mammalian fibroblasts in

culture

~20 hours

human liver cells ~1 year


• There are four stages of the cell cycle.

G1 Stage

S Stage

G2 Stage

M (Mitotic) Stage

Interphase


• Most of the cell cycle is spent in interphase.

G1 Stage (growth)

S Stage (synthesis)

G2 Stage (growth)

• Much happens during interphase to prepare the cell for cell division.


• G1 Stage:

– The cell recovers from the last division.

– The cell increases in size.

– The cell doubles its organelles.

– The cell accumulates materials that are necessary for DNA synthesis.

– The cell performs its necessary functions.


• G0 Stage?

– Cells that are permanently arrested are in the G0 stage.

– These cells perform their functions without preparing for cell division.

– These cells can resume the cell cycle in G1.

G0


• S Stage:

– Nuclear DNA replication (synthesis) occurs.

– Each chromosome is a double-helix of DNA.

– After DNA replication, each chromosome duplicates to form 2 identical double-helixes of DNA.

– Each double helix is called a chromatid.


• S Stage:

– The two, identical chromatids remain attached through a centromere until they are separated during mitosis.

– They are called sister chromatids.


• S Stage:

– Sister chromatids compose a duplicated chromosome.


• How many double helices of DNA compose a chromatid?

A. 0

B. 1

C. 2

D. 3

E. 4


• How many chromatids does a duplicated chromosome contain?

A. 0

B. 1

C. 2

D. 3

E. 4


• How many double helices does a duplicated chromosome contain?

A. 0

B. 1

C. 2

D. 3

E. 4


• How many chromatids compose the chromosomes of cells in G0?

A. 0

B. 1

C. 2

D. 3

E. 4


• G2 Stage:

– The cell prepares for cell division.

– The cell monitors the internal and external environments to determine if they are suitable for division.

G0


• Most of the cell cycle is spent in interphase.

G1 Stage (growth)

S Stage (synthesis)

G2 Stage (growth)

• Much happens during interphase to prepare the cell for cell division.

G0


• M Phase:

– mitosis (nuclear division)

– cytokinesis (cytoplasmic division)

• When M Phase is complete, two daughter cells are present.

G0

11.3 Control of the Cell Cycle

• The cell cycle is a tightly-controlled process.

• Proteins called cyclins assist with the progression of the cell cycle.

• The concentration of cyclins increases and decreases during the cell cycle.



• Cells must pass checkpoints to proceed through the cell cycle.

G0


• G1 checkpoint:

– Is the cell big enough?

– Are nutrients available?

– Is environment favorable?

– Is DNA intact?

G0


• G2 checkpoint:

– Is environment favorable?

– Is all DNA replicated?

– Is DNA intact?

G0


• M checkpoint:

– Are chromosomes ready for mitosis?

G0



• Cells must pass checkpoints to proceed through the cell cycle.

G0


• What happens first if a cell cannot proceed through a checkpoint?

A. The cell is arrested indefinitely.

B. The cell tries to fix the problem.

C. The cell becomes cancerous.

D. The cell undergoes cellular suicide.

E. The cellular contents are packaged and distributed to the surrounding tissue.


• What happens if the cell does not pass the checkpoints?

• The cell tries to fix the problem.

G0


• If the DNA is not intact, a protein called p53 attempts to initiate the repair of the DNA.

• This halts the cell cycle.

• If the DNA cannot be repaired, the cell then undergoes apoptosis.

G0

11.4 Cancer: Out-of-Control Cell Division

• Tumor-suppressor genes inhibit the cell cycle.

• Mutations in tumor-suppressor genes cause unregulated cell division.

• This is like brake failure in a car.


• p53 is an important tumor-suppressor protein.

• 50% of tumors have a mutated or deleted gene for p53.


• BRCA1 and BRCA2

– tumor-suppressor genes

– involved in the repair of double-stranded DNA breaks

– Mutations in BRCA1 or BRCA2 lead to highly penetrant breast and ovarian cancer phenotypes.


• If the DNA is not intact, a protein called p53 attempts to initiate the repair of the DNA.

• This halts the cell cycle.

• If the DNA cannot be repaired, the cell then undergoes apoptosis.

G0


• Apoptosis is programmed cell death.

apoptotic cellnecrotic cell


• Apoptosis is a controlled means of cell death.

• The cellular material is easily recycled after apoptosis.

• Apoptosis occurs frequently during development.


• Caspases are the enzymes that mediate apoptosis.

• Caspases are always present but inhibitors exist to prevent apoptosis until it is necessary.


• So, if cells ‘fail’ at any cell cycle checkpoint, they undergo apoptosis.

G0


• The cell cycle and apoptosis serve to maintain homeostasis in multi-cellular organisms.

G0

In-Class Discussion Questions

• Why would certain cells in your body need to replicate more often than others?

• What happens during interphase?

• Why would the cell cycle be a tightly-controlled process?

• When is apoptosis necessary?

11.2 How Does Mitosis Take Place?

• Mitosis is nuclear division.

• Cytokinesis is cytoplasmic division.

• Both are included in M stage.

• http://video.google.com/videoplay?docid=4045285854844480169#

G0


• Mitosis is nuclear division.

• Cytokinesis is cytoplasmic division.

• Both are included in M phase.

• http://video.google.com/videoplay?docid=4045285854844480169#

http://video.google.com/videoplay?docid=4045285854844480169




• The cell needs to accurately separate and distribute (segregate) the chromosomes during mitosis.

• The daughter cells must each receive an identical copy of the nuclear DNA from the parent cell.


• The cell assembles cytoskeletal components, called the spindle apparatus, that split the chromosomes and cytoplasm.

• Once the M stage is complete, the spindle apparatus disassembles.

• http://vimeo.com/15357750

• http://www.youtube.com/watch?v=m73i1Zk8EA0&feature=related

http://vimeo.com/15357750

http://vimeo.com/15357750

http://www.youtube.com/watch?v=m73i1Zk8EA0&feature=related




• The spindle apparatus is made up of centrosomes, microtubules, and protein motors.

• The centrosome is the microtubule-organizing center (MTOC) of the cell.

• The centrosome is duplicated during the preparation for mitosis.

• The mitotic spindle is made up of centrosomes, microtubules, and protein motors.

• The centrosome is the microtubule-organizin

• The centrosomes move to opposite poles of the cell.


• During nuclear division, the two sister chromatids separate at the centromere.

• The kinetochores are the site of microtubule attachment for chromosome separation.

• The spindle apparatus then separates the sister chromatids and the cytoplasm.


• The microtubules of the spindle apparatus attach to the centrosomes of chromosomes.

A. TRUE

B. FALSE


• Chromatin is composed of DNA, protein (histones), and some RNA.

• Chromatin appears as a tangled mass of threads when the cell is NOT dividing.


• Chromatin is composed of DNA, protein (histones), and some RNA.

• When the chromatin condenses, the double helix of DNA wraps around histones.


• Condensed chromatin is easily visible.


• The 5 phases of mitosis are

– Prophase

– Prometaphase

(Late Prophase)

–Metaphase

– Anaphase

– Telophase


• Prophase

– Centrosomes move away from each other.

– The spindle apparatus begins to assemble.

• Prophase

– Chromatin condenses.

– Chromosomes are easily visible.

– Nucleolus disappears.

– Nuclear envelope fragments.


• Prometaphase (Late Prophase)

– Kinetochores appear and attach to fibers of the spindle apparatus.

– The spindle apparatus fibers pull on the kinetochores of chromosomes to begin their alignment.


• Metaphase

– The centromeres of the chromosomes are aligned on a single plane in the center of the cell called the metaphase plate.

– The metaphase plate is the future axis of cell division.

– A checkpoint ensures that all chromosomes are attached properly.


• Metaphase

– The centromeres of the chromosomes are aligned on a single plane in the center of the cell called the metaphase plate.

– The metaphase plate is the future axis of cell division.

– A checkpoint ensures that all chromosomes are attached properly.

G0


• Anaphase

– The sister chromatids of chromosomes separate at the centromere.

– The fibers of the spindle apparatus attached to the kinetochores become shorter.

– The poles (centrosomes) move farther apart.

– Cytokinesis in animal cells begins with the formation of a cleavage furrow.


• Telophase

– The spindle apparatus disappears.

– New nuclear envelopes appear around the daughter chromosomes.

– The chromatin de-condenses.

– Nucleoli appear in the daughter cells.

– The cleavage furrow in animal cells becomes a more-defined contractile ring.



– Prophase

– Prometaphase

(Late Prophase)

–Metaphase

– Anaphase

– Telophase


• Cytokinesis (in animal cells)

– During anaphase, a cleavage furrow forms.

– During telophase, the cleavage furrow becomes a contractile ring.

– The contractile ring continues to contract around the parent cell to form the two daughter cells.


• Cytokinesis (in plant cells)

– The cell wall surrounding plant cell does not allow furrowing.

– Instead, a new cell wall is built in the middle of the parent cell.

In-Class i>clicker Questions

• In which phase of the cell cycle are sister chromatids pulled apart?

A. interphase

B. prophase

C. prometaphase

D. metaphase

E. anaphase

In-Class Discussion Questions

• Why would interphase chromatin (euchromatin) NOT be condensed?

• What is the difference between a centromere and a centrosome?

http://apps.nccd.cdc.gov/DCPC_INCA/DCPC_INCA.aspx

http://apps.nccd.cdc.gov/DCPC_INCA/DCPC_INCA.aspx


• Cancer is a cellular growth disorder that occurs when the control over cell division is lost.

• There are many causes of cancer, but most cancers result from the accumulation of mutations that permit cells to escape the normal controls of cell division.


• Most cancers begin as benign growths, growths that are not cancerous.

• Then, additional mutations occur. The cells are now malignant (cancerous and can spread).


• There are hallmark characteristics of cancer.

lack differentiation/immortal

abnormal nuclei

evade apoptosis

form tumors

undergo metastasis and angiogenesis


• Cancer cells lack differentiation/are immortal.

– They do not contribute to the functioning of a tissue.

– They look distinctly abnormal.

– They are immortal.

HeLa cellsHenrietta Lacks’ ovarian epithelial cancer cells


• Cancer cells have abnormal nuclei.

– Nuclei are enlarged.

– Nuclei contain an abnormal number of chromosomes.

– Portions of chromosomes can be deleted or repeated.

squamous cell carcinoma, ovarian cancer


• Cancer cells have abnormal nuclei.

– Nuclei are enlarged.

– Nuclei contain an abnormal number of chromosomes.

– Portions of chromosomes can be deleted or repeated.


• Cancer cells evade apoptosis.

– If the DNA is damaged, apoptosis usually occurs. Cancer cells do not undergo programmed cell death.


• Cancer cells form tumors.

– Normal cells exhibit contact inhibition – they stop dividing when they contact other cells.

– Cancer cells do not exhibit contact inhibition and grow in layers, forming tumors.


• Cancer cells undergo metastasis and angiogenesis.

– The additional mutations impart the ability to form new tumors distant from the site of the original tumor, or the ability to metastasize.

– Invasiveness is the defining feature of a malignant tumor.


• Cancer cells undergo metastasis and angiogenesis.

– The additional mutations impart the ability to form the blood vessels necessary to feed the growing mass of cells. This is called angiogenesis.



lack differentiation/immortal

abnormal nuclei

evade apoptosis

form tumors

undergo metastasis and angiogenesis



Many therapeutics aim to disrupt at least one of these hallmarks.

The trouble is often specifically targeting cancer cells and not normal cells.


• The normal growth and maintenance of tissues depend upon the balance between signals that promote and inhibit cell division.

• When this balance is upset, cancer can occur.

• Cancer usually results when there are mutations in genes that directly or indirectly affect this balance.


• Cancer is seldom due to a single defect.

• The combined damage is enough to break control over the cell cycle and induce uncontrolled growth and metastasis.

• Each cancer is due to a unique combination of errors.


• One day, there will most likely be a ‘magic bullet’ cure for all types of cancer.

A. TRUE

B. FALSE

Learning Outcomes

• After the study of this chapter and lecture notes, you should be able to…–discuss the need for asexual

reproduction,

–describe the stages of the cell cycle,

–describe the manifestation of cancer, and

–discuss the importance of control over the cell cycle.

The Cell Cycle

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Transcript of The Cell Cycle