Regulation of the Cell Cycle. Chapter 8-Part 3. Cell Cycle Check Points. The Cell Cycle has Go Ahead as well as Stop signals

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1 Regulation of the Cell Cycle Chapter 8-Part 3 Cancer Biology and Chromosomal Sorting Defects Cell cycle is regulated by a molecular control system The cycle has many important checkpoints Cell Cycle Check Points In a healthy system, s ONLY replicate their DNA and divide when proper signals tell them to do so Cell minding its own buisiness, being a stomach Cell received signal, replicated organelles and DNA, ready to divide The Cell Cycle has Go Ahead as well as Stop signals STOP GO Unregulated Cell Growth is Cancer A benign tumor A malignant tumor Metastasis Lymph vessels Tumor Glandular tissue Cell minding its own buisiness, being a stomach Cell received signal, replicated organelles and DNA, ready to divide A tumor grows from a single cancer. Cancer s invade neighboring tissue. Metastasis Cancer s spread through lymph and blood vessels to other parts of the body Figure 8.9 1

2 Cancer Treatment Slash, burn and poison Benign tumors can usually be removed surgically (slash) Radiation therapy disrupts division (burn) Chemotherapy involves drugs that disrupt division (poison) Radiation Therapy Some wavelengths of electromagnetic radiation causes breaks in DNA. DNA breaks can be lethal to s. Gamma rays X-rays UV Infrared Radiation will damage all exposed s. The more precise radiation treatment, the fewer side effects. Note, the same things that cause cancer can cure cancer. Why? Microwaves Radio waves What likely happened to poor Rosalind Franklin? How can electromagnetic radiation cause cancer? Electromagnetic radiation (from microwaves, to UV light, to X rays to gamma rays) can be absorbed by DNA molecules. DNA molecules can absorb photons, which can energize and break bonds!! These breaks happen all the time! Our s are pretty good (~97%) at fixing breaks Thymine Dimers caused by UV light 2

3 The Importance of DNA Repair Repair of damaged DNA is critical to longterm survival. Nucleotide extension repair Individuals with xeroderma pigmentosum make defective nucleotide excision repair enzymes. Without these repair enzymes, mutated DNA in skin s (UV) is not repaired, leading to skin cancers. Thymine Dimers Thymine dimers are an example of DNA damage repaired by this process Damaged part cut out by a nuclease Gap filled in with correct complementary pairs (using undamaged strand as template) DNA polymerase during DNA replication DNA Polymerases have an error rate of 1/10,000 base pairs (bp). Proofreading reduces the error rate of replication to 1/1 billion bp. Cells can repair many errors Humans have 130 known DNA repair enzymes! Chemotherapy Chemotherapy, in its crudest form, works by poisoning the body. Chemotherapeutics target RAPIDLY DIVIDING CELLS. Cancer s divide more rapidly then most of our normal s. The strategy, then, is to kill more cancer s than healthy s. Chemotherapeutics -How can they specifically target dividing s? -Why are there side effects to chemotherapy? -In what tissues of the body are the side effects most pronounced? Why?? Microtubules are very dynamic structures. They grow and shrink in a very, tightly regulated process. This process can be disrupted by drugs. Vinblastine: prevents spindle fiber from forming/growing. Taxol: prevents the dismantling of spindle fibers. 3

4 Thought questions: What stage of mitosis is Vinblastine first inhibiting??? Karyotyping Cells in mitosis treated with colchicine, a potent chemical that binds tubulin (the building block of microtubules), and blocks polymerization Spindle can t form, is frozen What stage of mitosis is Taxol inhibiting? Cell is smashed open Chromosomes are stained Snap shot/picture is taken Pictures of are literally cut out of picture, and arranged by size/shape (as pairs pairs that have duplicated!!) A karyotype is an orderly arrangement of Pair of homologous Centromere Sister chromatids Humans have Two different sex, X and Y 22 pairs of matching, called autosomes Homologous are matching pairs of Figure 8.12 When Meiosis Goes Awry What happens when errors occur in meiosis? How Accidents During Meiosis Can Alter Chromosome Number In nondisjunction The members of a chromosome pair fail to separate during anaphase This error results in gametes with an incorrect number of 4

5 Down Syndrome: An Extra Chromosome 21 The incidence of Down Syndrome increases with the age of the mother Is a condition where an individual has an extra chromosome 21 Is also called trisomy 21 Figure 8.19 The overall incidence of Down syndrome is only about 1 in 800 live births. Meiosis I The result of nondisjunction Nondisjunction Egg Meiosis II Nondisjunction Gametes n + 1 n + 1 n + 1 n -1 n -1 n + 1 n -1 n n Sperm Number of (a) Nondisjunction in meiosis I (b) Nondisjunction in meiosis II Figure 8.21 n (normal) Zygote 2n + 1 Figure 8.22 Abnormal Numbers of Sex Chromosomes Nondisjunction Also affects the sex Two kinds of sex chromosome abnormalities Breast development Poor beard growth Web of skin Constriction of aorta Poor breast develop ment Underdeveloped testes Underdeveloped ovaries Table 8.1 (a) A man with Klinefelter syndrome (XXY) (b) A woman with Turner syndrome (XO) Figure

6 Normal female karyotype Normal male karyotype Trisomy 21 (Down s Syndrome) Klinefelter s Syndrome (XXXXY) Is this a female or a male? XYY Males Normal features, tall stature and usually normal development The incidence of this condition is approximately one in 850 males. High levels of testosterone Hybrids. Rarely, two different species can successfully mate. 2 different chromosome numbers! The resulting offspring is almost always sterile 6

7 Liger= male lion + female tiger tigon or tiglon = male tiger + female lion mule = male donkey + female horse [horse:32chrom, donkey:31 chrom] hinny = male horse + female donkey (jenny) zorse = zebra + horse zonkey or zebrass = zebra + donkey (ass) cama = camel + llama catalo or beefalo = buffalo + cattle yakalo = yak + buffalo wholphin = whale + dolphin (specifically a false killer whale and a bottlenose dolphin) 7