Download Chapter 5 Cellular Functions

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Mutations
Chapter 5
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Most DNA mutations alter the protein product
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May…
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Cellular Functions
Make it function better (rarely)
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Change its function
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Reduce its function
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Make it nonnon-functional
Lecture 3: Cell Cycle and Cell Division
Mutations
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Example: Cancer
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Mutations in proteins that regulate cell
growth and division
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Unregulated cell growth
Cell Cycle
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To understand cancer, we need to understand
normal cell life cycle
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Begins and ends with division events
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Mitosis = process of division for most cells
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Interphase = time between division events
Cell Cycle
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Why do cells divide?
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Growth – allows a single fertilized egg to
become a relatively large multicellular
organism
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Adults have more cells than babies!
Cell Cycle
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Why do cells divide?
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Replacement– cells, like those of the skin,
Replacement–
wear out at a predictable pace
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Small intestine
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Cell Cycle
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Why do cells divide?
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Reproduction– most multicellular organisms
Reproduction–
produce egg and sperm cells that permit them
to produce offspring
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Meiosis – more on that later!
Cell Cycle
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Why do cells divide?
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Repair – accidents happen!
Cell Cycle
Interphase
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Interphase is the phase between cell divisions
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Cell spends most of its time here
Interphase has 3 stages as the cell prepares for
division
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Cell performs its functions here
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G1 phase – 8-12 hours (or longer)
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Transcription (chromatin unwound)
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“Growth 1” or “Gap 1” Phase
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Translation
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Cell manufactures cytoskeletal elements
and organelles for 2 cells
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Mitochondria divide
G0 Phase
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Exiting the cell cycle
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After G1, some cells enter a quiescent state
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Some rere-emerge after a time
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Some remain quiescent for the life of the
organism (muscle cells, neurons)
Interphase
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Interphase has 3 stages as the cell prepares for
division
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S phase – 6-8 hours
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“Synthesis” phase
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Chromosomes are duplicated
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Interphase
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Interphase has 3 stages as the cell prepares for
division
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M Phase
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G2 phase – 2-5 hours
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“Growth 2” phase
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Period of rapid cell growth and lastlast-minute
protein synthesis
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Cell is preparing to divide
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Some cells skip this stage
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Interphase ends when cells begin M phase
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“Mitosis” and cytokinesis
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Duplication and division of nucleus and the
entire cell
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Has its own steps (which we will cover in a
minute)
Frog embryos, cancer
Cell Cycle Checkpoints
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Exist to make sure a cell is healthy, normal
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Don’t want to duplicate mutated DNA!
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Three major checkpoints
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G1/S – check for sufficient growth, damaged
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G2/M – check for DNA damage in duplicated
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M – check for proper spindle formation just
DNA, sufficient preparations
chromosomes, is everything ready?
before cell divides
Cell Cycle Checkpoints
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Cyclin and cyclin
cyclin--dependent kinase
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Proteins involved in cell cycle regulation
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Depends on tumor suppressor called p53
p53 and Cancer
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Normal cell:
DNA
p53
Cell cycle
Damaged
Produced
Arrest
Repair
Cancer cell:
DNA
No p53
Uncontrolled
Damaged
Produced
Cell growth
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p53 and Cancer
Cancer
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p53 is frequently mutated in cancer
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Cancer treatments target rapidly dividing cells
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Cancer can occur in any tissue
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Problem: some normal cells divide rapidly
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Most common (National Cancer Institute)
1.
Prostate
2. Breast
3. Lung
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4. Colorectal
Mitosis
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Small intestine
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Cells for hair growth
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Bone marrow
Leads to common side effects of cancer
treatments
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Weight loss
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Hair loss
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Anemia
Repliclation (S phase)
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Primary type of cell division
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Helicase unwinds DNA strands
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Used by somatic cells
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Strands separate at replication fork
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Produces two genetically identical daughter cells
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Each strand used as a template
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Replication must occur prior to mitosis
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DNA polymerase makes missing strands
Replication fork
Replication fork
Repliclation (S phase)
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Two DNA strands are in opposite orientations
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Antiparallel
Problem: DNA polymerase can only add
nucleotides in one direction (5’ to 3’)
Replication fork
Repliclation (S phase)
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Leading strand synthesized continuously
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Lagging strand synthesized in short pieces that
are joined together
Replication fork
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Repliclation (S phase)
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Newly synthesized DNA molecules are called
Chromosomes
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Sister chromatids become attached to each
other at the centromere
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Condense to become chromosomes
chromatids
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Two identical molecules are called sister
chromatids
Chromosomes
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Chromosomes are large enough to be seen by
light microscope
Chromosomes are only present when a cell is
preparing to divide
Mitosis
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Takes place in several stages
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Do not memorize for this class, but someone will
want you to eventually (PMAT)
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In here: know the process of mitosis and what
steps must happen, without memorizing phase
names
Mitosis
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Prophase
Mitosis
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Metaphase
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Centrioles move to opposite poles
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Duplicated chromosomes line up at metaphase plate
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Nuclear membrane breaks down
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Microtubles attach to cenromeres at mitotic
spindle
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Additional checkpoint here
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Mitosis
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Anaphase
Mitosis
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Telophase
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Centromeres split
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Cell membrane constricts at center
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Half of chromosomes move toward each pole
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Cell membrane begins to pinch at center
Nuclear membranes rere-form around
chromosomes
Mitosis
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Cytokinesis
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Mitosis completed
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Two daughter cells with identical DNA
Mitosis
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Far more important than knowing the names for
each phase of mitosis is understanding what
happens to the DNA
Phase of the Cell Cycle
Human Cell Chromosome Number
Significant Event(s)
G1 (and G0)
S
Mitosis
Cytokinesis
46
92
92
46
Duplicate organelles
DNA replication
Sister chromosomes separate
Daughter cells produced
M phase
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