BIO 111 Lecture Unit 2 and Unit 3

What is cancer?

Cancer happens when the body is unable to control the division of cells. Cancerous cells divide uncontrollably and interfere with normal function. They don’t perorm their job and they stop non-cancerous cells from doing their job.

How are cancers named?

Cancer names reveal which organ or type of cell in which the cancer originated

Examples:

• Melanoma = skin pigment cells

• Leukemia = white blood cells in the bone marrow

• Carcinoma = lining of the internal organs or skin

• Sarcoma = connective tissue, such as bone

• Lymphoma = cells and tissues of the immune system

What is the MAJOR cause of the most common cancer in humans?

Smoking - lung and bronchus cancer

What are the five major characteristics of life?

1. Life processes energy:

   • obtains and uses energy from the environment

2. Life reproduces, grows, and develops:

   • all living organisms have genetic material and reproduce

   • growth and development is determined by genetic composition of the organism

     • development often heavily influenced by environment

3. Life is sensitive to stimuli:

   • sensitivity or response to stimuli

4. Life is capable of regulation:

   • homeostasis = maintain internal environment (pH, water, temperature, etc.)

5. Life adapts:

   • as an environment changes, natural selection causes the characteristics of a population to track those changes

What are the functions of each of the membrane-bound organelles discussed in lecture?

Nucleus:

• Acts as the genetic control center of the cell

• Stores hereditary information

Ribosomes

• Make proteins

• All prokaryotic and eukaryotic cells have ribosomes

Cytoskeleton

• Provides shape and support

• Controls intracellular traffic and enables movement

Lysosomes

• Act as floating garbage disposals for cells, digesting and recycling cellular waste products and consumed material

Endomembrane System (EMS)

• Composed of:

  • Rough Endoplasmic Reticulum (RER)

  • Smooth Endoplasmic Reticulum (SER)

  • Golgi Apparatus

• Function:

  • Produce and modify molecules for export to other parts of the organism

  • Break down toxic chemicals and cellular-by products

How is cell specialization achieved?

All cells in an individual have the same DNA

• Cells will only produce proteins from the DNA they need to do their specialized job

• “Gene expression”

Gene expression: What is gene expression?

Each cell has specific instructions about which proteins to produce (and how much)

• Cancer cells ignore these instructions

Gene expression: How could mutations lead to problems in enzyme pathways? How do problems in enzyme pathways lead to cancer?

• Order of amino acids determines all four levels of protein structures

  • Structure determines function

• Mutations are mistakes made during production that can lead to a non-functioning protein

• Most cellular processes require many different enzymes

• Even one non-functioning enzyme blocks the pathway

• Cancer occurs when the pathway in question relates to cell division

The Cell Cycle: The steps in the cell cycle in order

Interphase

• G1 (Cap/Growth 1): Cell grows

• S (Synthesis): DNA replicates

• G2 (Gap/Growth 2): Cells grows more

Mitotic phase

• Mitosis: copied chromosomes are moved into daughter cells

• Cytokinesis: Cell divides into two daughter cells

Interphase: G1

• Little visible change to cell

• Saves up energy

• Accumulates building blocks for DNA and proteins

• Cell growth and organelle duplication

Interphase: G0

• Inactive stage

• Cells are not actively preparing to divide

• Normal cell function

Interphase: S

• DNA replicates

• Forms two identcal copies of each chromosome

• Uses energy

Interphase: G2

• Preparation for mitosis

  • Cell replenishes energy

  • Cytoskeleton is dismantled

  • Cell growth

Mitotic: Miosis

Phases:

• Prophase:

  • Nuclear envelope disappears, provides access to the chromosomes

  • Nucleolus disappears, where ribosomes are made

  • Sister chromatids coil slightly and attach to mitotic spindles at the centromere

• Metaphase:

  • Chromosomes aligned in a middle plane called the metaphase plate

• Anaphase:

  • Sister chromatids are split apart at the centromere

    • Each side of the cell gets one set of homologues (one from dad’s genes, one from mom’s genes)

  • Cells become elongated

• Telophase

  • Events are reversed to make two cells

    • Chromosomes reach opposite poles and unravel

    • Mitotic spindles are broken down into monomers that will be used to assemble new cytoskeletons

    • Nuclear envelopes form around chromosomes

Mitotic: Cytokinesis

• Physical separation of the cytoplasmic components into two daughter cells

• A ring of actin fibers form and contract around edge of division

• Contracts and splits the cytoplasms of cells until they separate

The Cell Cycle: Checkpoints

The cell cycle has checkpoints to control division

• Regulte speed at which cell goes through cycle

• Ensure cell is ready for division

• Prevents compromised cells from continuing to divide

Cells that fail checkpoints go to G0 stage or undergo apoptosis (cell death)

Cell Cycle: G1 Checkpoint

• Checks for adequate cell size and energy reserves

• Checks DNA for damage

  • Important for cancer prevention

Cell Cycle: G2 Checkpoint

• Checks for adequate cell size and protein reserves

• Checks for complete chromosome replication and DNA damage

Cell Cycle: M Checkpoint

• Checks to ensure chromatids are ready for division and spindle fibers are properly built and attached

• If a cell does not meet all the requirements at each checkpoint, it will not progress to the next stage of the cell cycle

The Cell Cycle: What are the homologous chromosomes? What are sister chromatids? What’s a centromere?

Homologous: the maternal and paternal copies of a chromosome

Sister chromatid: one of the two identical copies of a chromosome created during replication

Centromere: holds the sister chromatids together

The Cell Cycle: What are telomeres? What happens to them as the cell undergoes more and more divisions? What enzyme do cancer cells use to avoid this?

Telomeres: ends of chromosomes, do not contain protein-coding DNA

• Gets shorter every time the chromosome is replicated

  • Once too short, cell undergoes apoptosis

Telomerase: Enzyme that lengthens telomeres

• Present in cancerous cells, preventing cell death

The Cell Cycle: What are centrioles and spindle fibers? What do they do during the cell cycle?

• Centriole: Organelles that make the spindle fibers out of microtubules

• Spindle Fibers: Organize chromosomes during cell division, split them evenly between daughter cells

What causes cancer?

What is a mutation? How can mutations cause no effects, abnormal proteins or incomplete proteins?

Mutation: permanent changes to DNA

Causes of cancer-causing mutations:

• Genetics: several genes known to increase risk of cancer

• Environment: radiation, chemicals, viruses

• Chance: DNA replication factor

Intro to DNA and Genetic Code

• DNA is double-stranded

• Each strand has a sequence of nucleotides

• A set of 3 nucleotides code for an amino acid

• The genetic code is redundant

  • Multiple codons lead to the same amino acid

  • Allows for flexibility with DNA mutations

What are tumor-suppressor genes? How many copies of a TS gene do you need for it to function properly?

• Tumor-suppressor gene: genes that code for proteins that examine DNA for damage at G1 checkpoint

  • STOP/SLOW cell cycle when functioning properly

• Need one functioning copy of TS gene to work

  • If you inherit a malfunctioning allele, one mutation leaves you without a TS gene in that cell

Two examples of TS genes

P53 Tumor-Suppressor Gene

• Activates DNA repair enzymes

  • Stops cell cycle and places cell in G0 phase

  • promotes apoptosis in unrepairable cells

• 50% of cancers are p53 mutations

BCRA1 Tumor-Suppressor Gene:

• Protein active

Unit 2 Module 2

What are the characteristics of cancer cells?

1. Different appearance

   • Cancerous cells are odd shapes, with larger nuclei that stain darker when looked at under a microscope

2. Unlimited cell division

   • Normal cells can divide a finite number of times

     • Telomerase and other innate controls

   • Cancer cells never lose their ability to divide

3. Less specialization

   • Mutations cause cells to stop expressing the correct proteins, losing function and specialization

4. Changes to blood flow

5. Invade surrounding tissues

   • a growing tumor can enroach on other cells and tissues, disrupting function, coopting resources, and even causing death

6. Move to other parts of the body

What is a tumor?

Mass of cells

What is angiogenesis?

Tumor releases growth factors, triggering nearby capillaries to grow toward the tumor

What is metastasis?

Cancer cells separate from a tumor and spread throughout the body via the circulatory or lymphatic systems

What are the characteristics of the four stages of cancer? How is each cancer stage determined?

• Size of tumor

• Whether tumor has invaded nearby tissues

• Whether cancer cells have spread to lymph nodes

• Whether cancer cells are present in other organ tissues

Stage 0,1

• Tumor is limited to a very small area

• Only lymph nodes very close to tissue have cancer cells (if any lymph nodes are involved at all)

Stage 2

• Tumor is larger and more invasive to surrounding tissues

  • Still entirely within its originating tissue though

• Lymph nodes may have cancer cells in them

Stage 3

• Tumor is larger and moved out of originating tissues, but not to distant organs

• Cancer cells detectable in lymph node tissues

Stage 4

Cancer is detectable in distant tissues outside originating area

What is homeostasis? How is it maintained?

Constant internal conditions maintained by body systems

• Temperature, pH, salt level, water level, bl

What are negative feedback loops?

1. Body senses abnormal condition

2. Body sends signals to control system

3. Body responds

4. Body returns to normal

5. Original signal stops

What are some examples from lecture? Which major system uses negative feedback loops to maintain homeostasis?

Water and salt balance

• kidney collects and filters fluids

• removes waste and regulates water/salt concentration in blood

• when water is high → less water concentration

• when water is low → more water concentration

Blood sugar balance

• pancreas regulates blood sugar levels

• when blood sugar is low → releases glucagon

Endocrine system

• system of glands that secrete hormones to maintain homeostasis

• hormones: chemicals that travel through blood and cause cellular responses in distant tissues

• hormones almost always function in negative eedback loops

How does cancer disrupt homeostasis?

• Tumors interfere with chemical signals

  • Prevent release by organs

  • Prevent transmission by blocking blood/lymphatic vessels

  • Prevent sense organs rom detecting abnormal condition

  • Prevent target organ from responding to signal

How does cancer alter body chemistry?

Bone cancer makes regulating blood calcium more difficult

• High blood calcium is dangerous

Liver cancer makes it hard to produce enzymes needed for digestion and blood sugar regulation

How does cancer disrupt organ function?

• Tumors disrupt oxygen flow to organs, take away other resources

• Tumors put pressure on parts of the brain that regulate important behaviors like breathing

Unit 2 Module 3

What are the ways cancer is diagnosed?

• Genetic testing

  • DNA test for known cancer-causing alleles

  • Blood draw → PCR → Sequence

• Blood tests

  • Number of white blood cells in blood

    • more WBCs means immune response

  • Tumor cells in blood if cancer is stage 4

  • Blood chemistry changes caused by cancer disrupting tissues

    • calcium, enzymes, ions

  • Presence of cancer-produced proteins

• Body scans

  • Breast cancer: mammogram

  • Other: CT, PET, MRI

What is chemotherapy? What is the major drawback of chemotherapy?

• Using drugs to kill or just stop division in cancer cels

• Drugs injected that interfere with cell cycle, which affects rapidly dividing cells more than others

• Drawback: many side effects because drugs affect all cells

What are the four major categories of chemotherapy drugs? Know how each works to stop cell division and the specific drawbacks of each.

Alkylating Agents

• Integrate into DNA, causing breaks in the strands

• Side effects: leukemia

Topoisomerase Inhibitors

• Disable topoisomerase enzyme, which unwinds DNA during replication

Antimetabolites

• Mimic nucleotides and can be integrated into DNA molecules

• Can’t work with DNA replication enzymes, preventing cell division

Alkaloids and Taxanes

• Block spindle fiber formation (alkaloids) or breakdown (taxanes)

  • prevents cell division from starting or ending

• Naturally produced by plants

Drawbacks: Nerve damage

What is radiation? What is radiation therapy? How is it used in cancer treatment?

• Movement of energy in waves or particles

• Shorter wavelengths have more energy

Radiation therapy

• Damages DNA within a cell, which slows or stops cell division

• Target specific tumor sites

  • less effective for metastatic cancers

What are some new types of treatments that are being used more and more?

Stem cell therapy

• Typically for blood-cell cancers

• Replace the bone marrow cells that create your red and white blood cells

Immunotherapy

• Use the body’s immune system to attack tumors

Genome editing

• Remove and replace cancer-causing genes

Unit 3 Module 1

What is a genetic disease?

Disease caused by mutation in DNA that is passed from parent to offspring

What is a gene? How are genes inherited?

Gene: unit of DNA that determines a trait

• Produces a protein, RNA, or other product

Inheritance

• Genes are inherited via sexual reproduction

• males produce sperm, females produce eggs

  • fusion of these gametes produces genetically distinct offspring

What is sickle-cell disease? Why is sickle-cell disease a good trait for studying genetics? What are the health consequences of sickle-cell disease?

• Mutation in gene that codes for protein (Hemoglobin) on red blood cells (RBCs) changes shape of RBCs from concave disc to a sickle

• Sickle-cell shape leads to myriad health problems caused by low access to oxygen

• Good trait for Studying Genetic Disease:

  • Single mutation leads to Sickle-Cell Disease (inheritance is straightforward)

  • Low incidence of genetic interactions changing the effect of the disease

  • Relatively free from environmental influence

What is hemoglobin and what is its structure?

• Protein complex composed of four polypeptide chains (globins)

• Four polypeptides each have a heme group with an iron (Fe) atom

• Up to 250 hemoglobin molecules per RBC

What are red blood cells? What do they do for you? What key eukaryotic cell feature do they lack and why?

• Deliver and exchange gases to body tissues

• Lack a nucleus, which makes the cell concave in shape and increases surface area for oxygen transfer

What is the structure and function of the circulatory system?

• Heart pumps blood around body in blood vessels to transfer oxygen to tissues

• Arteries: vessels where blood is moving away from the heart

• Veins: vessels where blood is moving toward the heart

What are the parts of the heart?

• Four chambered hearts

  • Top: Atria (singular = atrium)

  • Bottom: Ventricles

• Right side: Deoxygenated blood

• Left side: Oxygenated blood

What is the pathway of blood flow through the heart?

1. Deoxygenated blood enters right atrium on returm from body

2. Deoxygenated blood enters right ventricle

3. Deoxygenated blood is pumped to the lungs

4. Oxygenated blood returns to left atrium from lungs

5. Oxygenated blood enters let ventricle

6. Oxygenated blood is pumped through the Aorta to body from left ventricle

Where in the heart is blood oxygenated and deoxygenated?

• Oxygenated in lungs

• Deoxygenated in the body

How is blood pumped through the body?

• Lub: ventricles contract to pump blood out of heart

• Dub: atria contract to pump blood to ventricles

• Blood pressure measures force on artery walls when your heart is beating or between beats

What is the structured and function of the respiratory system? Where are gases exchanged in the lungs and in tissues?

• Breathe in oxygen (O2), breathe out Carbon Dioxide (CO2)

• Lungs are sequence of increasingly small branches that end in air sacs (alveoli) to maximize surface area for gas exchange

How are gases exchanged?

• Gases diffuse across cell plasma membranes according to concentration gradients

Sickle Cells in the Respiratory System

• Sickle-Cell Hemoglobin is misfolded, changing shape of cell, losing affinity for oxygen

  • Anemia: suite of symptoms caused by chronic low oxygen in body tissues

• Sickle-cell shape causes clumping and blockages in capillaries, reducing oxygen flow

  • Loses oxygen in area with blocks

• Sickle-cell block capillaries in the lungs, causing shortness of breath and fever

  • Lose oxygen flow to whole body because blood cannot reoxygenate

  • Sickle crisis

Unit 3 Module 2

Frederick Griffith Experiment

• Bacteria can transfer genetic information through a process he called transformation

• By injecting mice with a mixture of heat-killed lethal bacteria and live harmless bacteria, he demonstrated that the harmless strain acquired a “transforming principle” from the dead strain, becoming lethal and proving that genetic materia can be passed between organisms

• Identified DNA as the molecule for transferring hereditary characteristics, changing how scientists viewed bacterial genetics

Hershey and Chase

• DNA, not protein, is the genetic material that carries hereditary information.

• By using bacteriophage viruses, they demonstrated that only the DNA enters a bacterial cell to direct the production of new viruses, while the protein coat remains outside

Rosalind Franklin

DNA exists in a double-helix structure, with a sugar-phosphate backbone on the outside with bases on the inside

What is the structure of DNA?

• Complimentary strands

  • 5’ on one side 3’ on the other

• Base pairs

  • Adenine bonds with Thymine

  • Cytosine bonds with Guanine

• Double helix

• Antiparallel

  • 5’ → 3’ properties run in opposite directions

What molecules is DNA composed of?

• Nucleic acids: chains of nucleotides

  • phosphate group

  • five-carbon sugar (deoxyribose)

  • nitrogenous base

    • Adenine

    • Thymine

    • Guanine

    • Cytosine

What part of the molecules are the “sides” of the ladder vs the “rungs”

Backbone: alternating phosphate and deoxyribose sugar molecules

Rungs: two paired bases connected by hydrogen bonds

How are the molecules boded together to create a double helix?

What are the complimentary strands and what does it mean to be anti-parallel?

How is the human genome organized? What kinds of variation in sax chromosomes exist in humans?

• 46 chromosomes arranged in 23 pairs

  • 22 pairs of autosomes

  • 1 pair of sex chromosomes

• Two copies of each gene = Diploid

  • One copy from each ploidy

• Examples:

  • Turner Syndrome (XO)

  • Klinefelter Syndrome (XXY)

  • XYY Syndrome

  • Trisomy X Syndrome (XXX)

  • Androgen Insensitivity Syndrome (XY)

    • no testosterone receptor

What is DNA replication?

What are the steps in DNA replication?

1. Initiation

2. Elongation

3. Termination

DNA Replication: Initiation

Begins at origin of replication

• Special base sequences signaling enzymes to bind there for replication

DNA helicase binds to DNA and breaks hydrogen bonds between base pairs

• Forms replication fork with two separate strands

DNA Replication: Elongation

• A primer of complementary RNA bases binds to each strand

  • Removed at the end of replication and replaced with DNA

• DNA Polymerase adds new nucleotides

• DNA Polymerase can only read the DNA template in the 3’ to 5’ direction

• Therefore, DNA can only be built in the 5’ to 3’ direction

  • Leading strand

• The other strand’s 3’ end is not exposed when DNA replication begins

• This lagging strand must be made piece by piece

  • Okazaki fragments

DNA Replication: Termination

• RNA primers are removed and replaced with complementary DNA bases

• Okazaki fragments are sealed together with DNA ligase

Origin of replication

DNA helicase

DNA polymerase

DNA primers

Leading strand

Lagging strand

Okazaki fragments

DNA ligase

Telomeres

Telomerase

When are how does Proofreading occur?

DNA Polymerase proofreads and corrects errors during replication

When and how does Mismatch Repair occur?

• Occurs after replication

• Proteins detect, remove, and replace incorrect bases

When and how does Nucleotide excision repair occur?

• Required for more complex mistakes

  • Multiple incorrect bases

  • Thymine dimers

• DNA is unwound and the incorrect base(s), along with bases on 5’ and 3’ ends are removed and replaced

What is the structure of RNA? Which base from DNA is replaced by Uracil when RNA is transcribed?

• The sugar molecule in the RNA backbone contains an extra oxygen

• RNA has ony one sugar-phosphate backbone, while DNA has two

• Instead of thymine, RNA has a similar base called uracil

Steps of Transcription

1. Initiation

2. Elongation

3. Termination

Transcription: Initiation

• DNA double helix is partially unwound at site of transcription

  • Creates Transcription Bubble

• Enzymes/Proteins needed for transcription bind to promoter

  • Promoter tells enzymes how much to transcribe its corresponding gene

Transcription: Elongation

• RNA Polymerase builds an RNA strand that is complementary to the template strand in the 5’ to 3’ direction

• RNA is identical to non-template strand except all Thymines have been replaced with Uracils

• New RNA strand DOES NOT remain bound to DNA strand

• DNA is continuously unwound ahead of RNA polymerase and rewound behind it

Transcription: Termination

• Specific DNA sequences tell RNA Polymerase to stop transcribing and detach from the DNA template

Transcription bubble, Promotor, RNA polymerase, template strand, non-template strand

What is translation?

• Converting RNA into protein

• Occurs in ribosomes in cytoplasm and rough ER

• Requires:

  • Free amino acids (building blocks)

  • Ribosome units

  • Transfer RNA (tRNA)

What are the steps of translation?

1. Initiation

2. Elongation

3. Termination

Translation: Initiation

• Start codon on mRNA recognized by tRNA

• tRNA binds to ribosome subunits

• Ribosome assembles around mRNA