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Chapter 8: The Cell Cycle: the life cycle of cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cells divide and cells die • Each of a human’s trillions of cells retains the genetic information present in the fertilized egg – Every cell in the body results from countless rounds of cell division • Cells also die in predictable ways – Cell death is a normal part of development – Apoptosis – programmed cell death • Cell division and cell death must be in balance Chromosome duplication • A cell’s entire genome must be duplicated before cell division • In prokaryotic cells, genome is single circular DNA molecule • In eukaryotic cells, genome divided among multiple chromosomes housed in nucleus – Humans have 46, chickens 78, rice 24 Why is stem cell research so controversial? See p. 158-9 How is DNA used to clone a mammal like “Dolly” the sheep? See p. 160-1 Eukaryotic chromosomes • Chromatin – DNA plus packaging proteins – Nucleosomes – stretch of DNA wrapped around histones (proteins) • Chromatin barely visible when cell is not dividing – DNA loosely packed and accessible for cell • DNA condenses into visible chromosomes before cell division – Chromatid – one of 2 identical copies of a replicated chromosome – Sister chromatids – pair with identical DNA sequence – Centromere – point of attachment that holds sister chromatids together Chromosomes in humans • Most human cells have 46 chromosomes – – – – – – 23 from each parent; 46 total (23 pairs) Somatic or body cells Diploid – 2 full sets of genetic information Pair members look alike (not genetically identical) Except sex chromosomes, X and Y Produced by mitosis • Sperm and egg sex cells are haploid – 23 total chromosomes – Produced by germ cells in testes and ovaries – Produced by meiosis Human Karyotype: This is a chart called a Karyotype and it is used to display the chromosome pairs that an organism has…for humans a normal karyotype is 22 somatic pairs and 1 sex pair (either XX or XY depending on gender) If the karyotype is abnormal (missing or extra chromosomes), then the person has a “genetic abnormality” Ex: Turner’s Syndrome or Down Syndrome The Cell Cycle • Cell cycle – events between one cell division and the next • 2 major stages – Interphase – cell not dividing but cell very active – Cell division – mitosis and cytokinesis (cytoplasm division) The Cell Cycle • Interphase – Very active time in cell cycle – G1 – cell grows and carries out basic functions • Signals tell cell to divide, stop for repair of DNA, die or enter Go – S – genetic material replicates (DNA Replication) – G2 – cell prepares to divide and chromosomes begin to condense The Cell Cycle • Mitosis – Overall, separates genetic material evenly between 2 daughter cells – Mitotic spindle pulls half to each new cell – Centrosomes organize mitotic spindle – Kinetochores attach chromosomes to the spindle Phases of Mitosis • Prophase – chromosomes condense, mitotic spindle begins to form • Prometaphase – kinetochores grow on centromeres, nuclear envelop breaks down • Metaphase – chromosomes line up on mitotic spindle on equator • Anaphase – centromeres split, one chromatid of each pair pulled to opposite pole • Telophase – mitotic spindle disassembles, chromosomes begin to unwind, nuclear envelope reforms • Cytokinesis (differes in plant & animal cells because of cell wall in plant cells) – Animal cells – cleavage furrow results from contractile ring – Plant cells construct a new cell wall with cell plate Animal Cells Plant Cells Cell cycle regulation • Some cells divide more or less constantly • Signals to divide come from outside the cell • Growth factors – proteins stimulating cell division • Checkpoints – ensure cell does not enter next stage until previous stage complete • Telomeres – Tips of eukaryotic chromosomes – Lose nucleotides and become shorter at each cell division – Cell division stops after about 50 cell divisions – Most cells lack telomerase, the enzyme needed to add more DNA to extend telomeres • Teleomerase allows cells to go beyond 50 divisions – Present in some normal cells and cancer cells Cancer • Tumor – abnormal mass of tissue – Forms when body loses control of balance between cell division and cell death • Benign tumor – usually slow-growing and harmless • Malignant tumor –invades other tissues (metastasizes) – cancer Cancer • Cancer cells are not normal cells – Look different – Essentially immortal – May produce their own signals to divide – Lack contact inhibition – May not undergo apoptosis when damaged – Send signals to stimulate growth of blood vessels • Causes of Cancer – Oncogene abnormalities – abnormal variants of genes that normally control cell division • May accelerate cell cycle and cause cancer – Tumor suppressor gene abnormalities – encode proteins that normally block cancer development • Promote normal cell death or prevent cell division • Inactivation, deletion, or mutation can cause loss of function – Harmful chemicals, radiation, and viruses can alter DNA – Poor diet and exercise, sun exposure, and smoking can increase risk • Cancer treatments – Surgical tumor removal, chemotherapy, and radiation – Chemotherapy and radiation target rapidly dividing cell – both cancerous and healthy • Death of healthy cells cause side effects – New more targeted drugs home in on receptors for growth factors – Early detection key to successful treatment Cell death/Apoptosis • 2 main functions 1. Eliminates excess cells to carve out functional structures like fingers and toes 2. Weeds out cells that might harm the organism • Apoptosis must be overcome for mitosis to occur • Caspases – apoptosis-specific enzymes • Triggered when “death receptor” protein receives signal • Cuts apart cell’s proteins and destroys cell Investigating life: Cutting off a tumor’s supply lines in the war on cancer • Rapidly dividing cancer cells frequently develop resistance to drugs • Mutations allow some cancer cells to survive treatment and proliferate • Indirect attack of angiogenesis • Choke off tumor supply lines • 1997 – endostatin suppresses tumor growth in mice, no resistance, tumors never grew back – Clinical trials in humans yielded mixed results – Not unusual to find drug works well in animals but not humans