Chapter 11 How Cells Reproduce

11.1 Henrietta’s Immortal Cells Henrietta Lacks died of cancer in 1951, at age 31, but her cells (HeLa cells) are still growing in laboratories HeLa cells are widely used to investigate cancer, viral growth, and other processes important in medicine and research Understanding the structures and mechanisms that cells use to divide help us understand why cancer cells are immortal and we are not

HeLa Cells Figure 11.1 HeLa cells, an immortal legacy of cancer victim Henrietta Lacks (right). The fluorescence micrograph (left) shows some of the internal components of two HeLa cells in the process of dividing. Blue and green indicate the location of two proteins that help microtubules (red) attach to chromosomes (white). Defects in these and other proteins that orchestrate cell division result in descendant cells with too many or too few chromosomes, an outcome that is a hallmark of cancer.

11.2 Multiplication by Division Division of a eukaryotic cell typically occurs in two steps: nuclear division followed by cytoplasmic division The sequence of stages through which a cell passes during its lifetime is called the cell cycle A sequence of three stages (interphase, mitosis, and cytoplasmic division) through which a cell passes between one cell division and the next

The Eukaryotic Cell Cycle cytoplasmic division mitosis G2 S i n t e r p h a s G1 A cell spends most of its life in interphase, which includes three stages: G1, S, and G2. telophase anaphase metaphase prophase G1 is the phase of growth before DNA replication. The cell’s chromosomes are unduplicated. S is the phase of synthesis, during which the cell makes copies of its chromosome(s) by DNA replication. G2 is the phase after DNA replication and before mitosis. The cell prepares to divide during this stage. The nucleus divides during mitosis, the four stages of which are detailed in the next section. After mitosis, the cytoplasm may divide. Each descendant cell begins the cycle anew, in interphase. Built-in checkpoints stop the cycle from proceeding until certain conditions are met. Figure 11.2 The eukaryotic cell cycle. The length of the intervals differs among cells. G1, S, and G2 are part of interphase. 1 A cell spends most of its life in interphase, which includes three stages: G1, S, and G2. 2 G1 is the phase of growth before DNA replication. The cell’s chromosomes are unduplicated. 3 S is the phase of synthesis, during which the cell makes copies of its chromosome(s) by DNA replication. 4 G2 is the phase after DNA replication and before mitosis. The cell prepares to divide during this stage. 5 The nucleus divides during mitosis, the four stages of which are detailed in the next section. 6 After mitosis, the cytoplasm may divide. Each descendant cell begins the cycle anew, in interphase. Built-in checkpoints stop the cycle from proceeding until certain conditions are met.

Interphase Interphase consists of three stages, during which a cell increases in size, doubles the number of cytoplasmic components, and replicates its DNA G1: Interval of cell growth and activity S: Interval of DNA replication (synthesis) G2: Interval when the cell prepares for division

Interphase and the Life of a Cell Most cell activities take place during G1 Control mechanisms work at certain points in the cell cycle Most cell cycle checkpoints are in the stages of interphase Some can keep cells in G1 Loss of control may cause cell death or cancer

Mitosis and Asexual Reproduction Mitosis is a nuclear division mechanism that maintains the chromosome number In multicelled species, mitosis and cytoplasmic division increase cell number during development, and replace damaged or dead cells later in life In asexual reproduction, a single individual can reproduce by mitosis and cytoplasmic division

Homologous Chromosomes Pairs of chromosomes having the same length, shape, and genes Typically, one member of a pair is inherited from the mother, the other from the father Human cells have 46 chromosomes (23 pairs) Except for a pairing of sex chromosomes (XY) in males, the chromosomes of each pair are homologous

A An unduplicated pair of chromosomes in a cell in G1. B By G2, each chromosome has been duplicated. Figure 11.4 How mitosis maintains the chromosome number. C Mitosis and cyto-plasmic division package one copy of each chromosome into each of two new cells. Stepped Art

How Mitosis Maintains the Chromosome Number 6 Mitosis and cytoplasmic division package one copy of each chromosome into each of two new cells. 2 Pair of homologous chromosomes in a cell during G1. Both are unduplicated. 4 By G2, each chromosome has been duplicated. Figure 11.4 How mitosis maintains the chromosome number.

Chromosomes During Division A cell cannot function without a full complement of DNA Each cell needs to have one copy of each chromosome The cell replicates its DNA in preparation for mitosis

Stages of Mitosis Four stages of mitosis parcel sister chromatids into separate nuclei Prophase Metaphase Anaphase Telophase Cytoplasmic division results in two diploid cells, each with the same number and kind of chromosomes as the parent

Controls Over the Cell Cycle Most differentiated human cells are in G1 – some types never progress past that stage When a cell divides is determined by gene expression controls Some cause the cell cycle to advance Others stop the cycle from proceeding These built-in checkpoints allow problems to be corrected before the cycle proceeds

11.3 A Closer Look at Mitosis When a nucleus divides by mitosis, each new nucleus has the same chromosome number as the parent cell What are the four stages of mitosis?

Preparing for Mitosis During interphase, a cell’s chromosomes are loosened to allow transcription and DNA replication In preparation for nuclear division, chromosomes condense into their most compact “X” forms Tight condensation keeps the chromosomes from getting tangled and breaking during nuclear division

Interphase and Early Prophase Plant cell nucleus Animal cell nucleus 4 Metaphase All of the chromosomes are aligned midway between the spindle poles. 5 Anaphase Spindle microtubules separate the sister chromatids and move them toward opposite spindle poles. Each sister chromatid has now become an individual, unduplicated chromosome. Figure 11.5 Mitosis. Micrographs show nuclei of plant cells (onion root, left), and animal cells (fertilized eggs of a roundworm, right). A diploid (2n) animal cell with two chromosome pairs is illustrated.

Prophase What happens during prophase? Centrosome Chromosomes condense Microtubules form a bipolar spindle Nuclear envelope breaks up Microtubules attach to the chromosomes Centrosome A region near the nucleus that organizes spindle microtubules; usually includes two centrioles

Mitosis – Prophase 6 Telophase Plant cell nucleus Animal cell nucleus 6 Telophase The chromosomes reach opposite sides of the cell and loosen up. Mitosis ends when a new nuclear envelope forms around each cluster of chromosomes. Figure 11.5 Mitosis. Micrographs show nuclei of plant cells (onion root, left), and animal cells (fertilized eggs of a roundworm, right). A diploid (2n) animal cell with two chromosome pairs is illustrated.

The Spindle A dynamic network of microtubules that forms during nuclear division Grows into the cytoplasm from opposite poles of the cell and attaches to duplicated chromosomes Microtubules from opposite poles attach to different sister chromatids and separate them

The Spindle – Illustrated spindle pole © Conly L Rieder Figure 11.6 The spindle. In this dividing lung cell of a salamander, microtubules (green) have extended from two centrosomes to form the spindle, which has attached to and aligned the chromosomes (blue) midway between its two poles. Red shows actin microfilaments.

Metaphase and Anaphase All duplicated chromosomes line up midway between the spindle poles Anaphase Microtubules separate the sister chromatids of each chromosome and pull them to opposite spindle poles

Mitosis – Metaphase and Anaphase Plant cell nucleus Animal cell nucleus 4 Metaphase All of the chromosomes are aligned midway between the spindle poles. 5 Anaphase Spindle microtubules separate the sister chromatids and move them toward opposite spindle poles. Each sister chromatid has now become an individual, unduplicated chromosome. Figure 11.5 Mitosis. Micrographs show nuclei of plant cells (onion root, left), and animal cells (fertilized eggs of a roundworm, right). A diploid (2n) animal cell with two chromosome pairs is illustrated. left, Michael Clayton/University of Wisconsin, Department of Botany; right, ISM/Phototake; far right, © Cengage Learning.

Telophase During telophase: Two clusters of chromosomes reach the spindle poles A new nuclear envelope forms around each cluster Two new nuclei are formed, each with the same chromosome number as the parent cell

Mitosis – Telophase 6 Telophase Plant cell nucleus Animal cell nucleus 6 Telophase The chromosomes reach opposite sides of the cell and loosen up. Mitosis ends when a new nuclear envelope forms around each cluster of chromosomes. Figure 11.5 Mitosis. Micrographs show nuclei of plant cells (onion root, left), and animal cells (fertilized eggs of a roundworm, right). A diploid (2n) animal cell with two chromosome pairs is illustrated. left, Michael Clayton/University of Wisconsin, Department of Botany; right, ISM/Phototake; far right, © Cengage Learning.

11.4 Cytokinesis: Division of Cytoplasm In most kinds of eukaryotes, the cell cytoplasm divides between late anaphase and the end of telophase, but the mechanism of division differs between plants and animals Cytokinesis The process of cytoplasmic division

Cytokinesis in Animal and Plant Cells Animal cells A cleavage furrow partitions the cytoplasm A band of actin filaments rings the cell midsection, contracts, and pinches the cytoplasm in two Plant cells A cell plate forms midway between the spindle poles Partitions the cytoplasm when it reaches and connects to the parent cell wall

Cytoplasmic Division in Animal Cells Animal cell cytokinesis 1 In a dividing animal cell, the spindle disassembles as mitosis ends. 2 At the midpoint of the former spindle, a ring of actin and myosin filaments attached to the plasma membrane contracts. 3 This contractile ring pulls the cell surface inward, forming a cleavage furrow as it shrinks. Figure 11.7 Cytoplasmic division of animal cells and plant cells. 4 The ring contracts until it pinches the cell in two.

Cytoplasmic Division in Plant Cells Plant cell cytokinesis 5 In a dividing plant cell, vesicles cluster at the future plane of division before mitosis ends. 6 The vesicles fuse with each other, forming a cell plate along the plane of division. 7 The cell plate expands out- ward along the plane of division. When it reaches and attaches to the plasma membrane, it parti- tions the cytoplasm. Figure 11.7 Cytoplasmic division of animal cells and plant cells. 8 The cell plate matures as two new cell walls. These walls join with the parent cell wall, so each descendant cell becomes enclosed by its own wall.

11.5 Marking Time With Telomeres The ends of eukaryotic DNA strands consist of noncoding sequences called telomeres Telomeres protect eukaryotic chromosomes from losing genetic information at their ends Vertebrate telomeres have a short DNA sequence, 5′-TTAGGG-3′, repeated thousands of times Shortening telomeres are associated with aging

Telomeres Telomeres are important because a polymerase can’t copy the last hundred or so bases of the 3′ end of a chromosome When telomeres get too short, checkpoint gene products stop the cell cycle, and the cell dies

Stem Cells and Telomerase In an adult, only stem cells retain the ability to divide indefinitely What are stem cells immortal? They retain the ability to make telomerase, a molecule that reverses the telomere shortening that normally occurs after DNA replication Research suggests that the built-in limit on cell divisions may be part of the mechanism that sets an organism’s life span

Telomeres – Illustrated Figure 11.8 Telomeres. The bright dots at the end of each DNA strand in these duplicated chromosomes are telomeres.

11.6 When Mitosis Becomes Pathological When enough checkpoint mechanisms fail, a cell loses control over its cell cycle forms a neoplasm – a group of cells that lost control over how they grow and divide A neoplasm that forms a lump (abnormal mass) in the body is called a tumor

Oncogenes and Proto-Oncogenes An oncogene is any gene that helps transform a normal cell into a tumor cell Genes encoding proteins that promote mitosis are called proto-oncogenes – mutations can turn them into oncogenes Growth factors are molecules that stimulate a cell to divide and differentiate A gene that encodes the epidermal growth factor (EGF) receptor is an example of a proto-oncogene

Oncogenes and Overactive EGF Receptors Figure 11.9 Effects of an oncogene. In this section of human breast tissue, a brown-colored tracer shows the active form of the EGF receptor. Normal cells are lighter in color. The dark cells have an overactive EGF receptor that is constantly stimulating mitosis; these cells have formed a neoplasm.

Tumor Suppressors Checkpoint gene products that inhibit mitosis are called tumor suppressors because tumors form when they are missing The products of the BRCA1 and BRCA2 genes are examples of tumor suppressors – they regulate the expression of DNA repair enzymes Viruses such as HPV (human papillomavirus) cause cells to make proteins that interfere with their own tumor suppressors

Checkpoint Genes in Action Figure 11.10 Checkpoint genes in action. Radiation damaged the DNA inside this nucleus. A Red dots show the location of the BRCA1 gene product. B Green dots pinpoint the location of the product of a gene called 53BP1. Both proteins have clustered around the same chromosome breaks in the same nucleus; both function to recruit DNA repair enzymes. The integrated action of these and other checkpoint gene products blocks mitosis until the DNA breaks are fixed. A B © Phillip B. Carpenter, Department of Biochemistry and Molecular Biology, University of Texas - Houston Medical School.

Cancer Benign neoplasms (such as ordinary skin moles) grow slowly, stay in one place, and are not cancerous Malignant neoplasms (cancers) disrupt body tissues, both physically and metabolically Get progressively worse Dangerous to health Cancer causes 15-20% of all human deaths in developed countries

Three Characteristics of Cancer Cells Cancer cells grow and divide abnormally Capillary blood supply to the cells may increase abnormally Cytoplasm and plasma membrane are altered Malignant cells typically have an abnormal chromosome number Metabolism may shift toward fermentation Altered or missing proteins impair the function of the plasma membrane

Three Characteristics of Cancer Cells (cont’d.) Cancer cells break loose and invade other parts of the body (metastasis) Due to altered recognition proteins and weakened adhesion, they do not stay anchored properly in tissues Can slip easily into and out of circulatory and lymphatic systems vessels Use these vessels to migrate elsewhere in the body

Neoplasms and Malignancy Benign neoplasms grow slowly and stay in their home tissue. Cells of a malignant neoplasm can break away from their home tissue. The malignant cells become attached to the wall of a lymph vessel or blood vessel (as shown here). They release digestive enzymes that create an opening in the wall, then enter the vessel. The cells creep or tumble along inside vessels, then exit the same way they got in. Migrating cells may start growing in other tissues, a process called metastasis. Figure 11.11 Neoplasms and malignancy

Reducing the Risk of Cancer Life style choices can reduce the risk of acquiring mutations that lead to cancer Not smoking, avoiding exposure of unprotected skin to sunlight, etc. Some neoplasms can be detected with periodic screening procedures such as gynecology or dermatology exams

Skin Cancers C Melanoma spreads fastest. Cells form dark, encrusted lumps that may itch or bleed easily. B Squamous cell carcinoma is the second most common form of skin cancer. This pink growth, firm to the touch, grows under the skin’s surface. A Basal cell carcinoma is the most common type of skin cancer. This slow-growing, raised lump may be uncolored, reddish-brown, or black. (A) Dr. Allan Harris/Phototake; (B) Biophoto Associates/Science Source; (C) James Stevenson/Science Source. Figure 11.12 Skin cancer can be detected with early screening. A Basal cell carcinoma is the most common type of skin cancer. This slow-growing, raised lump may be uncolored, reddish-brown, or black. B Squamous cell carcinoma is the second most common form of skin cancer. This pink growth, firm to the touch, grows under the skin’s surface. C Melanoma spreads fastest. Cells form dark, encrusted lumps that may itch or bleed easily.

Points to Ponder Exactly where and when does mitosis occurs in any organism? What would happen if cytokinesis did not occur in plants and animals? Many of the drugs used in chemotherapy cause loss of hair in the individual being treated. Why is this?