Chapter 4 Cancer DNA Synthesis Mitosis and Meiosis

Chapter 4 Cancer DNA Synthesis, Mitosis, and Meiosis Fourth Edition BIOLOGY Science for Life | with Physiology Colleen Belk • Virginia Borden Maier © 2013 Pearson Education, Inc. Copyright © 2009 Pearson Education, Inc. Power. Point Lecture prepared by Jill Feinstein Richland Community College

Why should we care about mitosis? §Our cells go through cell division (mitosis) to grow and repair tissues § This process is highly regulated: § The DNA must make a copy and that copy is closely “proofread” § The cell must receive proper signals to grow or repair tissues in order to start the division process § If the process becomes unregulated, this can lead to uncontrolled growth - cancer © 2013 Pearson Education, Inc.

1 What Is Cancer? § Cancer is a disease of deregulation and evolution § Tumor: Unregulated cell division that form a mass of cells with no function § Benign tumor: doesn’t affect surrounding tissues or cause disease § Malignant tumor: invades surrounding tissues and causes disease; cancerous § Metastasis: cells break away from a malignant tumor and start a new cancer at another location © 2013 Pearson Education, Inc.

1 What Is Cancer? © 2013 Pearson Education, Inc.

1 What Is Cancer? § Cancer cells differ from normal cells: § Cancer cells divide when they shouldn’t § Cancer cells invade surrounding tissues and cause disease § Cancer cells move to other locations in the body © 2013 Pearson Education, Inc.

1 What Is Cancer? § Metastatic cells can travel throughout the body via the lymphatic system or the circulatory system. § Lymphatic system collects fluid, waste and loose cells that are present in our tissues. § Lymph nodes filter the lymph that flows through the lymphatic system before the lymph returns to the circulatory system. § Cancer cells found in lymph nodes indicate metastasis is occurring (why? ). § Once in either system, the cancer cells can travel anywhere in the body © 2013 Pearson Education, Inc.

1 What Is Cancer? § Risk factors: increase a person’s risk of developing a disease (Table 6. 1) § Tobacco use: tobacco contains many carcinogens (especially burnt tobacco) § High-fat, low-fiber diet (improves bodily absorption of DNA -modifying chemicals) § Weakened immune system from: § Alcohol consumption • Obesity § Lack of exercise • Increasing age • chronic suppression • HIV/AIDS § Overdivsion of cells (stomach, skin, ovary, testicles, prostate) § Genetic factors (breast cancer, retinoblastoma) § Viral infection (Epstein-Barr virus, HPV, KSHV) © 2013 Pearson Education, Inc.

Is Cancer Developing? hange in bowel or bladder habits sore that does not heal nusual bleeding or discharge hickening or lump ndigestion or difficulty swallowing bvious change in wart or mole agging cough or hoarseness Copyright © 2010 Pearson Education, Inc.

Mitosis and Meiosis §Our cells go through cell division (mitosis) to make new cells when growth or repair is required § Result is 2 cells with diploid number of chromosomes § In humans that is 46 chromosomes §Another division process (meiosis) happens in cells that will make gametes (egg and sperm cells) § Result is egg and sperm cells that have half the number of chromosomes § In humans that is 23 chromosomes § Egg and sperm fuse to reform 46 chromosomes © 2013 Pearson Education, Inc.

2 Passing Genes and Chromosomes to Daughter Cells § Asexual reproduction: § Only one parent § Offspring are genetically identical to parent § No shuffling of DNA, i. e. “shuffling of the deck” § Sexual reproduction § Gametes (egg cells and sperm cells) are combined from two parents § Offspring are genetically different from one another and from the parents, “shuffling of the deck” © 2013 Pearson Education, Inc.

Molecular aspects of gene and trait passage § Before dividing, cells must copy their DNA § Gene: section of DNA that has the instructions for making a specific protein and conferring a specific function or trait to the organism § One molecule of DNA is wrapped around proteins to form a chromosome containing hundreds to thousands of genes. § Different species have different numbers and sizes of chromosomes (we have 46). © 2013 Pearson Education, Inc.

2 Passing Genes and Chromosomes to Daughter Cells § Chromosomes are uncondensed before cell division (like piles of spaghetti or balls of unwound yarn) Immediately before division © 2013 Pearson Education, Inc. Between divisions

2 Passing Genes and Chromosomes to Daughter Cells § Chromosomes are duplicated through DNA replication § Duplicated chromosomes, held together at the centromere, are called sister chromatids © 2013 Pearson Education, Inc.

2 Passing Genes and Chromosomes to Daughter Cells § DNA molecule is a double stranded structure similar to a twisted ladder. § The sides of the ladder are composed of a sugar-phosphate backbone. § Nucleotides are connected to each other by hydrogen bonding to form the “rungs” of the ladder. § Adenine (A) pairs with thymine (T) § Cytosine (C) pairs with Guanine (G) § For a video, please click this link. Focus on why pairing works and on the structural features mentioned above © 2013 Pearson Education, Inc.

HOW is DNA replicated so exactly? ? ? § DNA molecule is split up the middle of the helix § Nucleotides are added to each side via hydrogen bonding § Result is two identical daughter molecules, each with one parental strand one new strand (semiconservative replication) © 2013 Pearson Education, Inc.

2 Passing Genes and Chromosomes to Daughter Cells § DNA polymerase: the enzyme that replicates DNA § It moves along the length of the unwound DNA and helps form the new strands © 2013 Pearson Education, Inc.

2 Passing Genes and Chromosomes to Daughter Cells Understand the difference between sister chromatids (identical) and homologous chromosomes (the near copies)! © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis § Cell cycle has three steps: § Interphase: the cell grows, DNA replicates § Mitosis: the copied chromosomes are split and sister chromatids are moved in opposite directions § Mitosis occurs in somatic or body cells. § Cytokinesis: the cell is split into 2 daughter cells, each containing the full complement of (now) unduplicated chromosomes © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Interphase § Mitosis generally takes only an hour to complete § Interphase has three phases: § G 1: cell grows, organelles duplicate (11 hours to decades!) § S: DNA replicates (8 hours) § G 2: cell makes proteins needed to initiate and complete mitosis (4 hours) § Most of the cell cycle is spent in interphase © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Mitosis § Mitosis produces genetically-identical daughter nuclei § Mitosis is followed by cytokinesis which splits the two nuclei into two daughter cells § Four stages, each to be discussed in separate slides: § Prophase – chromosomes condense § Metaphase – chromosomes move to midline § Anaphase – chromosomes separate to poles § Telophase – chromosomes relax © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Mitosis § Prophase: § Chromosomes condense § Nuclear envelope disappears § Microtubules pull the chromosomes around during cell division § Animal cells: microtubules attached to centrioles at the poles of the cell © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Mitosis § Metaphase: § Chromosomes are aligned across the middle of the cell by microtubules § A “quality control” check is done to make sure chromosomes are aligned properly © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Mitosis § Anaphase: § centromeres split, § sister chromatids are pulled apart toward opposite poles • Telophase: • Nuclear envelopes reform around clustered chromosomes • Chromosomes revert to uncondensed form © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Mitosis © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Mitosis © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Cytokinesis § Cytokinesis (in animals) is the stage in which proteins pinch the cell into two halves § two daughter cells are formed from the original one; each having its own nucleus § After cytokinesis, cells reenter interphase. © 2013 Pearson Education, Inc.

3 The Cell Cycle and Mitosis - Cytokinesis § Cytokinesis in Plants: § Starts with vesicles forming the cell plate. § Cell walls made in vesicles § This results in a new cell wall being formed with the fused vesicles between the cells forming daughter cells’ plasma membranes. § The cell wall is made from cellulose © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation § Cell division is a tightly controlled process § Normal cells halt at checkpoints § “Quality control/Quality assurance” § Proteins survey the condition of the cell § Cell must pass the survey to proceed with cell division § 3 checkpoints: G 1, G 2, and metaphase § Cancers often “cheat” and skip several cell cycle checkpoints © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation • Are microtubules from one side grabbing only one sister chromatid? © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation § Growth factors stimulate cells to divide when conditions are right § Growth factors bind to receptors to trigger a response from a cell § Mutation: a change in the sequence of DNA § Changes to DNA can change the structure and function of the protein coded by the DNA § Changes to DNA can change how genes are expressed § Mutations may be inherited, caused by carcinogens, or (more rarely) caused by natural errors (1: 108/division) © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation § Proto-oncogenes: genes that promote cancer development if they are altered § When proto-oncogenes mutate, they become oncogenes § Most are involved in controlling growth and mitosis § Altered proteins no longer properly regulate cell division § Altered proteins usually overstimulate cell division © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation § Tumor suppressor genes: genes for proteins that stop cell division if conditions are not favorable § When mutated (usually inactivated), can allow cells to more easily override checkpoints © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation § Depending on the number of mutations and whether the tumor suppressor protein is functional will determine whether it is a benign or malignant tumor that is formed. © 2013 Pearson Education, Inc.

4 Cancer Development Requires Many Mutations § Progression from benign tumor to cancer requires many mutations. § Angiogenesis: tumor gets its own blood supply § Loss of contact inhibition: cells will now pile up on each other in a given tissue § Loss of anchorage dependence: enables a cancer cell to move to another location when overcrowded § Immortalized: cells no longer have a fixed number of cell divisions due to an enzyme called telomerase © 2013 Pearson Education, Inc.

4 Cell Cycle Control and Mutation – Multiple Hit Model § Most genes need to have both copies of a particular gene mutated to become cancerous. § Multiple hit model: process of cancer development requires multiple mutations on multiple genes § Some mutations may be inherited (familial risk); usually one of two copies are already “hit”. Loss of heterozygosity ruins the second copy § Most mutations are probably acquired during a person’s lifetime © 2013 Pearson Education, Inc.

5 Cancer Detection and Treatment § Early detection increases odds of survival § There are different detection methods for different cancers § Some cancers produce increased amount of a characteristic protein (often those needed to survive in the body) § Biopsy: surgical removal of cells or fluid for analysis § Needle biopsy: removal is made using a needle § Laparoscope: surgical instrument with a light, camera, and small scalpel (minimally invasive) © 2013 Pearson Education, Inc.

5 Cancer Detection and Treatment - Treatment Methods § Chemotherapy: drugs that selectively kill dividing cells § Combination of different drugs used (“cocktail”) § Interrupt cell division in different ways § Multiple drugs helps prevent resistance from individual drugs from arising easily § Normal dividing cells are also killed (hair follicles, bone marrow – immune system, stomach lining) © 2013 Pearson Education, Inc.

5 Cancer Detection and Treatment - Treatment Methods § Radiation therapy: use of high-energy particles to destroy cancer cells § Damages their DNA so they can’t continue to divide or grow § Usually used on cancers close to the surface § Typically performed after chemotherapy “shrinks” the tumor and surgical removal of tumor remnant § If a person remains cancer free after treatment for 5 years they are in remission and after 10 years they are cured. § Improved early detection and new biotechnologies have greatly increased survival rate if remission fails © 2013 Pearson Education, Inc.

6 Meiosis § Specialized form of cell division in gonads to produce gametes § Reduces number of chromosomes in each cell by one-half § Chromosomes come in homologous pairs § Gamete gets one of each pair © 2013 Pearson Education, Inc.

6 Meiosis § Chromosomes can be visualized using a karyotype. § Human somatic cells have 22 pairs of autosomes and one pair of sex chromosomes © 2013 Pearson Education, Inc.

6 Meiosis § Gametes are haploid or have 1 set of 23 chromosomes § When the egg and sperm nuclei fuse it forms a zygote which is diploid § Somatic or body cells are also diploid © 2013 Pearson Education, Inc.

6 Meiosis § Starts with interphase – DNA is duplicated § Meiosis takes place in two stages: § Meiosis I § Separating the homologous pairs into 2 separate cells (sister chromatids REMAIN TOGETHER!) § Meiosis II § Separating the sister chromatids in each cell to produce 4 haploid cells. © 2013 Pearson Education, Inc.

6 Meiosis I © 2013 Pearson Education, Inc.

6 Meiosis II © 2013 Pearson Education, Inc.

6 Meiosis § Crossing over: exchange of equivalent portions of chromosomes between members of a homologous pair § Sister chromatids identified by enzymes seeking similar DNA strands § Strands are “knotted together” to ensure that sister chromatids are paired up before they are split up § “unknotting” produces crossing over § Results in new types of gametes being formed § Linked genes (neighbors) typically cross over together § Random alignment: the way in which different pairs of chromosomes align and get separated during meiosis I is random § Results in different types of gametes being formed © 2013 Pearson Education, Inc.

6 Meiosis - Mistakes in Meiosis § Nondisjunction: failure of homologues to separate normally during meiosis (nothing is perfect…) § Results in a gamete having one too many chromosomes (trisomy) or one too few chromosomes (monosomy) § Most embryos that result from such gametes will die before birth (gene imbalance is too unstable) § Several chromosome abnormalities are known in humans (Table 6. 2) © 2013 Pearson Education, Inc.

© 2013 Pearson Education, Inc.

Autosomal and sex-linked chromosomal anomalies Copyright © 2010 Pearson Education, Inc.

Autosomal and sex-linked chromosomal anomalies Copyright © 2010 Pearson Education, Inc.

The Male calico cat Copyright © 2010 Pearson Education, Inc.

6 Comparison of Mitosis and Meiosis A does not care to find a B does not care to find b © 2013 Pearson Education, Inc. A MUST find a B MUST find b

6 Meiosis § For cancer mutations to be passed on to offspring, they must take place in cells that give rise to gametes. § Mutations caused by environmental exposures are not passed on unless the mutation occurs in the gametes. § Mutations in somatic cells (e. g. , skin cancer from UV ray exposure) are not heritable. © 2013 Pearson Education, Inc.

Which of following statements incorrectly identifies how cancer cells differ from normal cells? § Cancer cells divide when they should not. § Cancer cells invade surrounding tissues. § Cancer cells form benign tumors. § Cancer cells can move to other locations in the body. © 2013 Pearson Education, Inc.

Which of following statements incorrectly identifies how cancer cells differ from normal cells? § Cancer cells divide when they should not. § Cancer cells invade surrounding tissues. § Cancer cells form benign tumors. § Cancer cells can move to other locations in the body. © 2013 Pearson Education, Inc.

How many chromosomes does a human body cell contain? § 12 § 23 § 34 § 46 © 2013 Pearson Education, Inc.

How many chromosomes does a human body cell contain? § 12 § 23 § 34 § 46 © 2013 Pearson Education, Inc.

Which statement correctly describes the role of DNA polymerase in DNA replication? § DNA polymerase splits the double-stranded DNA in half. § DNA polymerase helps bind incoming nucleotides to each other. § DNA polymerase lines up chromosomes on the metaphase plate. § DNA polymerase helps prevent the degradation of chromosomes. © 2013 Pearson Education, Inc.

Which statement correctly describes the role of DNA polymerase in DNA replication? § DNA polymerase splits the double-stranded DNA in half. § DNA polymerase helps bind incoming nucleotides to each other. § DNA polymerase lines up chromosomes on the metaphase plate. § DNA polymerase helps prevent the degradation of chromosomes. © 2013 Pearson Education, Inc.

During which phase of mitosis does the centromere split, allowing motor proteins to pull each sister chromatid to opposite poles of the cell? § prophase § metaphase § telophase § anaphase © 2013 Pearson Education, Inc.

During which phase of mitosis does the centromere split, allowing motor proteins to pull each sister chromatid to opposite poles of the cell? § prophase § metaphase § telophase § anaphase © 2013 Pearson Education, Inc.

A gene encoding a protein that regulates the G 1 checkpoint is mutated What is a likely outcome? § Tumors will develop. § The cell will die. § The cell will live but never divide. § The cell will become larger and large. © 2013 Pearson Education, Inc.

A gene encoding a protein that regulates the G 1 checkpoint is mutated What is a likely outcome? § Tumors will develop. § The cell will die. § The cell will live but never divide. § The cell will become larger and large. © 2013 Pearson Education, Inc.

The genes that encode the proteins regulating the cell cycle are called ____. § oncogenes § proto-oncogenes § carcinogens § malignant © 2013 Pearson Education, Inc.

The genes that encode the proteins regulating the cell cycle are called ____. § oncogenes § proto-oncogenes § carcinogens § malignant © 2013 Pearson Education, Inc.

True or False: Chemotherapy causes hair loss because hair follicles divide rapidly, like cancer cells. § True § False © 2013 Pearson Education, Inc.

True or False: Chemotherapy causes hair loss because hair follicles divide rapidly, like cancer cells. § True § False © 2013 Pearson Education, Inc.

At what stage of meiosis does crossing over occur? § metaphase II § prophase II © 2013 Pearson Education, Inc.

At what stage of meiosis does crossing over occur? § metaphase II § prophase II © 2013 Pearson Education, Inc.

A checkpoint is missing from this picture. Where is this checkpoint? § at the beginning of G 2 § at the end of M phase § during S phase § at the end of G 2 © 2013 Pearson Education, Inc.

A checkpoint is missing from this picture. Where is this checkpoint? § at the beginning of G 2 § at the end of M phase § during S phase § at the end of G 2 © 2013 Pearson Education, Inc.

What does this figure show? § centromere § karyotype § cancerous cells § animal cells of different sizes © 2013 Pearson Education, Inc.

What does this figure show? § centromere § karyotype § cancerous cells § animal cells of different sizes © 2013 Pearson Education, Inc.