THE CELL CYCLE Chapter 8 Picture is of Dolly, a clone. Procedure involved transferring the nucleus of a specialized cell (in this case a mammary gland cell) into an egg cell whose nucleus had been removed. Chapter 8

A. The Cell Cycle Events that occur in the life of a cell. Includes 3 major stages: Interphase Karyokinesis (mitosis) Cytokinesis Karyokinesis & cytokinesis can overlap in time, depending upon the species.

1. Interphase Cell is not dividing. G1 Phase - carries out basic functions & performs specialized activities. duration is extremely variable contains restriction checkpoint ~ cell “decides” to: - divide - enter a quiescent phase (G0) - die “G” stands for “gap” or “growth”

S Phase - cell replicates chromosomes & synthesizes proteins. G0 Phase - cell maintains specialized characteristics, but does not divide. Ex. neurons & muscle cells S Phase - cell replicates chromosomes & synthesizes proteins. “S” stands for “synthesis” Replicated chromosome consists of 2 sister chromatids (exact copies of chromosomal material). Sister chromatids are joined together at a small section of the DNA sequence called the centromere. [animal cells replicate centrioles as well]

G2 Phase - cell synthesizes additional proteins (ex G2 Phase - cell synthesizes additional proteins (ex. tubulin) & assembles/stores membrane material. Large amounts of tubulin will be required to form microtubules of mitotic spindle. Illustration = animal cell in G2 interphase. Photo = plant cell in G2 interphase.

2. Karyokinesis (mitosis; M phase) Equal distribution of replicated genetic material. Mitosis is a continuous process; is considered in stages for ease of understanding.

Prophase replicated chromosomes condense* centrosomes separate & migrate toward opposite sides of cell mitotic spindle forms (microtubules grow out from centrosomes) nucleolus disappears Illustration = animal cell in Prophase. Photo = plant cell in Prophase. *Remember, chromosomes were replicated during S phase of interphase. Centrosome = cloud of proteins (& centrioles in animal cells) that organizes the mitotic spindle.

Prometaphase nuclear membrane breaks down spindle fibers attach to centromeres of chromosomes Once attached, the chromosomes begin moving along the spindle fibers toward the equator of the mitotic spindle. Illustration = animal cell in Prometaphase. Photo = plant cell in Prometaphase.

Metaphase chromosomes are lined up single-file along equator of mitotic spindle. Illustration = animal cell in Metaphase. Photo = plant cell in Metaphase.

Anaphase centromers part, sister chromatids (now called chromosomes) separate chromosomes move toward opposite poles Illustration = animal cell in Anaphase. Photo = plant cell in Anaphase.

Telophase mitotic spindle breaks down chromosomes decondense nuclear membranes reform around two nuclei nucleoli reappear Illustration = animal cell in Telophase. Photo = plant cell in Telophase.

3. Cytokinesis Distribution of cytoplasm to daughter cells. begins during anaphase or telophase differs in animal & plant cells Cytokinesis overlaps with karyokinesis. It begins during anaphase or telophase depending upon species or cell type.

Cytokinesis in animal cells: cleavage furrow (slight indentation) forms around equator of cell. actin & myosin microfilaments act like a drawstring to pinch the cell in two. usually an equal division.

Cytokinesis in animal cells

Cytokinesis in plant cells: phragmoplast (microtubule structure) forms in cytoplasm & traps vesicles containing cell wall material. vesicles fuse, forming a cell plate across midline of cell. cell plate gives rise to two primary cell walls.

Does cytokinesis always accompany karyokinesis? Karyokinesis in the absence of cytokinesis results in a syncytium (mass of multinucleated cells). Usually, but not always. Examples: human skeletal muscle tissue (pictured) endosperm tissue in some plants (nourishes the developing embryo in a seed).

Control of the Cell Cycle Checkpoints - groups of interacting proteins that ensure cell cycle events occur in the correct sequence. Various mechanisms interact to regulate the cell cycle. Are numerous checkpoints - 4 are described in figure. Restriction checkpoint - cell “decides” whether to divide, enter G0 phase, or die. Most important checkpoint. DNA damage checkpoint - turns on genes that manufacture proteins that repair damaged DNA. Apoptosis checkpoint - necessary to override a signal for the cell to die. Spindle assembly checkpoint - necessary for construction of spindle & binding of chromosomes to it.

Shortening of telomeres - loss of telomere DNA signals cell to stop dividing. Some cells produce telomerase (enzyme that continually adds telomere DNA). Telomeres are repeating nucleotide sequences found at the tips of chromosomes. Every time a cell divides, some of its telomere DNA is lost. After about 50 divisions (Hayflick limit), a key amount of lost telomere DNA signals cell division to cease. NOTE: Cells that produce telomerase are able to divide beyond the 50-division limit. They include: plant cells cells lining small intestine bone marrow cells certain immune system cells sperm-forming cells cancer cells

Contact Inhibition - healthy cells stop dividing when they come in contact with other cells.

Hormones - stimulate cell division. Ex. Estrogen stimulates uterine cell division Growth factors - proteins that stimulate local cell division. Ex. Epidermal growth factor (EGF) stimulates epithelial cell division filling in new skin underneath a scab Interaction of kinases & cyclins - activate genes that stimulate cell division.

B. Apoptosis Programmed cell death; part of normal development. Example of apoptosis: Feet of embryonic chickens & ducks have webbing between the toes. Webbing vanishes as the chicken’s foot develops (due to apoptosis). Webbing is retained as duck’s foot develops. Apoptosis fine-tunes the human immune system - in the fetus, it destroys T cells that do not recognize self. If they were not destroyed, these T cell would begin attacking the body (autoimmune disease).

Steps of Apoptosis: Death receptors activate enzymes called capases. Capases destroy proteins & various cell components & ready the cell for phagocyte destruction. From outside, cell rounds up, forms bulges called blebs and fragments (fragments are surrounded by cell membrane, so they don’t initiate an inflammatory response). Cell death in response to an injury is called necrosis. The cell swells & bursts, initiating an inflammatory response.

C. Cancer (loss of cell cycle control) Condition resulting from excess cell division or deficient apoptosis. Characteristics of Cancer Cells: can divide uncontrollably & eternally are heritable & transplantable lack contact inhibition readily metastasize exhibit angiogenesis exhibit genetic mutability Cancer cells can divide eternally because they produce telomerase. Cervical cancer cells (HeLa) of Henrietta Lacks who died in 1951 are used extensively in cancer research all over the world today. Heritability - when a cancer cell becomes cancerous, it passes its loss ov cell cycle control to its descendants. Transplatability - cancer cells can be injected into a healthy animal; animal will develop cancer because those cancer cells divide to form more cancerous cells. Cancer cells lack contact inhibition - they tend to form masses called tumors. Metastasize = ability to spread Angiogenesis = ability to induce local blood vessel formation. Cancer cells mutate - a treatment that shrank the original tumor may have no effect on its subsequent growth.

Causes of Cancer: Over-expression of oncogenes Oncogenes are genes that trigger limited cell division. Inactivation of tumor suppressor genes Tumor suppressor genes prevent a cell from dividing or promote apoptosis. Oncogenes are normally switched off in most cells. They are activated only under certain circumstances (ex. in cells at wound site). Tumor suppressor genes are normally switched on in most cells. If they are inactivated or removed cells will divide continually or apoptosis does not occur (ex. a childhood kidney cancer is caused by absence of a tumor suppressor gene that normally halts mitosis in kidney tubule cells in the fetus) Factors that turn on oncogenes or turn off tumor suppressor genes at inappropriate times would lead to development of tumors.

Normal functioning of oncogenes & tumor suppressor genes may be affected by environmental factors: carcinogens radiation viruses diet exercise habits Carcinogens = chemicals that cause cancer (tobacco, asbestos, insecticides, saccharine) Radiation - UV & x-ray photons have enough energy to cause DNA damage.