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.

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. B. C. D. E.

meiosis mitosis binary fission nuclear fission cytokinesis

11.1 Mitosis and the Cell Cycle • 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.

11.1 Mitosis and the Cell Cycle • 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.


11.1 Mitosis and the Cell Cycle • Cells divide to produce identical daughter cells for three reasons: – growth – wound repair – asexual reproduction

11.1 Mitosis and the Cell Cycle • 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


11.1 Mitosis and the Cell Cycle • There are four stages of the cell cycle. G1 Stage S Stage G2 Stage

Interphase

M (Mitotic) Stage

11.1 Mitosis and the Cell Cycle • There are four stages of the cell cycle. G1 Stage S Stage G2 Stage

Interphase

M (Mitotic) Stage

11.1 Mitosis and the Cell Cycle • 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.

11.1 Mitosis and the Cell Cycle • 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.

11.1 Mitosis and the Cell Cycle • 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

11.1 Mitosis and the Cell Cycle • 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 doublehelixes of DNA. – Each double helix is called a chromatid.

11.1 Mitosis and the Cell Cycle • S Stage: – The two, identical chromatids remain attached through a centromere until they are separated during mitosis. – They are called sister chromatids.

11.1 Mitosis and the Cell Cycle • S Stage: – The two, identical chromatids remain attached through a centromere until they are separated during mitosis. – They are called sister chromatids.

11.1 Mitosis and the Cell Cycle • S Stage: – Sister chromatids compose a duplicated chromosome.

In-Class i>clicker Question • How many double helices of DNA compose a chromatid? A. B. C. D. E.

0 1 2 3 4

In-Class i>clicker Question • How many chromatids does a duplicated chromosome contain? A. B. C. D. E.

0 1 2 3 4

In-Class i>clicker Question • How many double helices does a duplicated chromosome contain? A. B. C. D. E.

0 1 2 3 4

In-Class i>clicker Question • How many chromatids compose the chromosomes of cells in G0? A. B. C. D. E.

0 1 2 3 4

In-Class i>clicker Question • How many chromatids compose the chromosomes of cells in G0? A. B. C. D. E.

0 1 2 3 4


11.1 Mitosis and the Cell Cycle • 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

11.1 Mitosis and the Cell Cycle • 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

11.1 Mitosis and the Cell Cycle • 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 tightlycontrolled process. • Proteins called cyclins assist with the progression of the cell cycle. • The concentration of cyclins increases and decreases during the cell cycle.

11.3 Control of the Cell Cycle • The cell cycle is a tightly-controlled process. • Cells must pass checkpoints to proceed through the cell cycle.

G0

11.3 Control of the Cell Cycle • G1 checkpoint: – Is the cell big enough? – Are nutrients available? – Is environment favorable? – Is DNA intact?

G0

11.3 Control of the Cell Cycle • G2 checkpoint: – Is environment favorable? – Is all DNA replicated? – Is DNA intact?

G0

11.3 Control of the Cell Cycle • M checkpoint: – Are chromosomes ready for mitosis?

G0

11.3 Control of the Cell Cycle • The cell cycle is a tightly-controlled process. • Cells must pass checkpoints to proceed through the cell cycle.

G0

In-Class i>clicker Question • What happens first if a cell cannot proceed through a checkpoint? A. B. C. D. E.

The cell is arrested indefinitely. The cell tries to fix the problem. The cell becomes cancerous. The cell undergoes cellular suicide. The cellular contents are packaged and distributed to the surrounding tissue.

11.3 Control of the Cell Cycle • What happens if the cell does not pass the checkpoints? • The cell tries to fix the problem.

G0

11.3 Control of the Cell Cycle • 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 tumorsuppressor genes cause unregulated cell division. • This is like brake failure in a car.

11.4 Cancer: Out-of-Control Cell Division • p53 is an important tumor-suppressor protein. • 50% of tumors have a mutated or deleted gene for p53.

11.4 Cancer: Out-of-Control Cell Division • 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.

11.3 Control of the Cell Cycle • 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

11.3 Control of the Cell Cycle • Apoptosis is programmed cell death.

necrotic cell

apoptotic cell

11.3 Control of the Cell Cycle • Apoptosis is a controlled means of cell death. • The cellular material is easily recycled after apoptosis. • Apoptosis occurs frequently during development.

11.3 Control of the Cell Cycle • Apoptosis is a controlled means of cell death. • The cellular material is easily recycled after apoptosis. • Apoptosis occurs frequently during development.


11.3 Control of the Cell Cycle • Caspases are the enzymes that mediate apoptosis. • Caspases are always present but inhibitors exist to prevent apoptosis until it is necessary.

11.3 Control of the Cell Cycle • So, if cells ‘fail’ at any cell cycle checkpoint, they undergo apoptosis.

G0

11.3 Control of the Cell Cycle • 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/vide oplay? docid=404528585484448016 9#

G0

11.2 How Does Mitosis Take Place? • Mitosis is nuclear division. • Cytokinesis is cytoplasmic division. • Both are included in M phase. • http://video.google.com /videoplay?docid=404528 5854844480169#

11.2 How Does Mitosis Take Place? • 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.

11.2 How Does Mitosis Take Place? • 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.

11.2 How Does Mitosis Take Place? • 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/15357 750

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

11.2 How Does Mitosis Take Place? • The spindle apparatus is made up of centrosomes, microtubules, and protein motors.

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

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

• The centrosome is the microtubule-organizin

• The centrosome is duplicated during the preparation for mitosis.

• The centrosomes move to opposite poles of the cell.

11.2 How Does Mitosis Take Place? • 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.

In-Class i>clicker Question • The microtubules of the spindle apparatus attach to the centrosomes of chromosomes. A. TRUE B. FALSE

11.2 How Does Mitosis Take Place? • Chromatin is composed of DNA, protein (histones), and some RNA. • Chromatin appears as a tangled mass of threads when the cell is NOT dividing.

11.2 How Does Mitosis Take Place? • Chromatin is composed of DNA, protein (histones), and some RNA. • When the chromatin condenses, the double helix of DNA wraps around histones.

11.2 How Does Mitosis Take Place? • Chromatin is composed of DNA, protein (histones), and some RNA. • When the chromatin condenses, the double helix of DNA wraps around histones.

11.2 How Does Mitosis Take Place? • Condensed chromatin is easily visible.

11.2 How Does Mitosis Take Place? • Condensed chromatin is easily visible.


11.2 How Does Mitosis Take Place? • The 5 phases of mitosis are – Prophase – Prometaphase (Late Prophase) – Metaphase – Anaphase – Telophase

11.2 How Does Mitosis Take Place? • Prophase – Chromatin condenses. – Chromosomes are easily visible. – Nucleolus disappears. – Nuclear envelope fragments.

• Prophase – Centrosomes move away from each other. – The spindle apparatus begins to assemble.

11.2 How Does Mitosis Take Place? • 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.

11.2 How Does Mitosis Take Place? • 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.

11.2 How Does Mitosis Take Place? • 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

11.2 How Does Mitosis Take Place? • 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.

11.2 How Does Mitosis Take Place? • 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 moredefined contractile ring.

11.2 How Does Mitosis Take Place? • The 5 phases of mitosis are – Prophase – Prometaphase (Late Prophase) – Metaphase – Anaphase – Telophase

11.2 How Does Mitosis Take Place? • The 5 phases of mitosis are

11.2 How Does Mitosis Take Place? • 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.

11.2 How Does Mitosis Take Place? • 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. B. C. D. E.

interphase prophase prometaphase metaphase 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

11.4 Cancer: Out-of-Control Cell Division • 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.

11.4 Cancer: Out-of-Control 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).

11.4 Cancer: Out-of-Control Cell Division • There are hallmark characteristics of cancer. lack differentiation/immortal abnormal nuclei evade apoptosis form tumors undergo metastasis and angiogenesis

11.4 Cancer: Out-of-Control Cell Division • Cancer cells lack differentiation/are immortal. – They do not contribute to the functioning of a tissue. – They look distinctly abnormal. – They are immortal.

HeLa cells Henrietta Lacks’ ovarian epithelial cancer cells

11.4 Cancer: Out-of-Control Cell Division • 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

11.4 Cancer: Out-of-Control Cell Division • Cancer cells have abnormal nuclei. – Nuclei are enlarged. – Nuclei contain an abnormal number of chromosomes. – Portions of chromosomes can be deleted or repeated.

11.4 Cancer: Out-of-Control Cell Division • Cancer cells evade apoptosis. – If the DNA is damaged, apoptosis usually occurs. Cancer cells do not undergo programmed cell death.

11.4 Cancer: Out-of-Control Cell Division • 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.

11.4 Cancer: Out-of-Control Cell Division • 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.

11.4 Cancer: Out-of-Control Cell Division • 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.

11.4 Cancer: Out-of-Control Cell Division • There are hallmark characteristics of cancer. lack differentiation/immortal abnormal nuclei evade apoptosis form tumors undergo metastasis and angiogenesis

11.4 Cancer: Out-of-Control Cell Division • There are hallmark characteristics of cancer. Many therapeutics aim to disrupt at least one of these hallmarks. The trouble is often specifically targeting cancer cells and not normal cells.

11.4 Cancer: Out-of-Control Cell Division • 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.

11.4 Cancer: Out-of-Control Cell Division • 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.

In-Class i>clicker Question • 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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