CELL CYCLE

Prokaryotic Cell Division

 Prokaryotic cells reproduce asexually  Binary fission

Eukaryotic Cells
 Somatic Cells
o Cells that make your organs and tissues
 Sex Cells
o The ONLY cells that are not somatic – sperm and egg (Gametes)
Cell Division
 In Eukaryotes, cell division occurs in two major stages.
o The first stage, division of the cell nucleus, is called mitosis
o The second stage, division of the cell cytoplasm, is called cytokinesis
 The cell cycle is the series of events that cells go through as they grow and divide.
 Interphase, is the period of growth that occurs between cell division
o Cell spends most of its life in this phase

 Must copy and package DNA in nucleus before cytoplasm

 During the cell cycle:
o A cell grows
o It is pre-paired for division
o It divides to form two daughter cells, each of which begins the cycle again
There are two types of Cell Division
 Mitosis:
o Produces 2 genetically identical cells
o Happens throughout body
o One part of the cell cycle
o Growth, cell replacement, tissue repair
 Also used for asexual reproduction = Organisms close elves
o Unique to eukaryotes
 Meiosis:
o Produces 4 genetically different cells
o Cells only have ½ of genetic information
o Happens only in gonads
The Cell Cycle consist of four phases:
 G1 (First Gap Phase)
 S phase
 G2 (Second Gap Phase)
 M Phase
Cells that pass the restriction point in the G1 phase will progress through the cell cycle and
divide. By contrast, non-dividing cells can enter the G0 phase and can reversibly re-enter the
cell cycle or become quiescent, losing the ability to cycle and sometimes becoming
senescent.

Events of the Cell Cycle

 During G1, the cell
o Increases in size (cell grows)
o Synthesizes new proteins and organelles (Cell develops)
 During the S phase, (DNA replication)
o Chromosomes are replicated
o DNA synthesis takes place
o Once a cell enters the S phase, it usually completes the rest of the cell cycle
 The G2 Phase (Second Gap Phase)
o Organelles and molecules required for cell division are produced
o Once G2 is complete, the cell is ready to start the M phase- Mitosis
Cell cycle has a “life cycle”
 Cell is formed from a mitotic division
o Cell grows and matures to divide again  G1, S, G2, M  Epithelial cells,
blood cells, stem cells
LIVER CELLS

o Cell grows and matures to never divide again  G1 to G0  Brain/nerve cells

Cells stay in G1 if making macromolecules, they enter S when DNA and accessory proteins
are copied and the rate of DNA replication is same for all cells of a species

DNA
 Chromatin – long, thin strands made up of DNA and protein. The protein helps the
DNA to stay together when chromosomes form
 Chromosomes – Genetic information is passed from one generation to the next on
chromosomes. Before cell division, each chromosome is duplicated, or copied.
Chromosomes – Condensed Chromatin

 Chromosomes are made of DNA molecules

 Each chromosome consists of two identical “sister” chromatids. Each pair of
chromatids is attached at an area called the centromere
 During mitosis, 2 sister chromatids (duplicated chromosomes) separate
 Each becomes independent chromosomes that end up in 1 daughter cell

Mitosis – Cell Division

 Occurs in body cells – somatic cells
 Forms two identical daughter cells – exactly like the original
 Biologists divide the events of mitosis into four phases: (PMAT)
o Prophase: First, and longest phase of mitosis.
 The centrioles separate and take up positions on opposite sides of
the nucleus
 The centrioles lie in a region called the centrosome. The
centrosome helps to organize the spindle, a fanlike microtubule
structure that helps separate the chromosomes.
o Metaphase:
 The second phase of mitosis is metaphase (shortest phase)
 The chromosomes line up across the center of the cell.
 Microtubules connect the centromere of each chromosome to the
poles of the spindle
 Summary: Chromosomes attach to spindle fibers in center of the
cell
o Anaphase:
 The third phase of mitosis.
 The sister chromatids separate into individual chromosomes.
 The chromosomes continue to move until they have separated
into two groups.
 Summary: Centromeres split apart and chromatids separate from
one another. Each chromatid moves to opposite poles.
o Telophase:
 Chromosomes reach opposite poles of cell
 Chromatids unwind back into chromatin
 Nuclear envelope and nucleolus reappear reforming the nucleus
 Spindle fibers disappear
 New double membrane (cell membrane ) gain to form between 2
nuclei (cell pinches)
 Animal cell – cleavage
 Plant cell – cell plate
 The Mitotic Spindle: Present in every cell.
o Made of microtubules = change length by addition or removal of tubulin
subunits
o Originates from pair of centrioles
 Cytokinesis – Cytoplasm Division
o During cytokinesis, the cytoplasm pinches in half.
o Each daughter cell has an identical set of duplicate chromosomes
  Early in cell division, duplicated chromosome is condensed = coils up
 DNA winds twice around histones = nucleosome
 Keeps chromosomes organized during nuclear division

Genome is also
checked
  The cell cycle is the series of events that cells go through as they grow and divide
 Interphase is the period of growth that occurs between cell divisions
 Cell spends most of its life in this phase
Chromosome number
 Humans have 46 chromosomes = diploid (2n)
 2 of each type of chromosome = one set from mother, one from father
 During mitosis:
o Each 2n parent cell produces two 2n daughter cells
o Each daughter cell has each pair of chromosomes = 23 pairs
o Summary of mitosis: Nuclear and cellular division that maintains
chromosome number. Used for growth, repair, asexual reproduction
Cell Division and DNA replication is regulated so that:
 DNA only replicated once before cell division
 Cells that never divide do not replicate DNA
 Cells don’t try to replicate DNA if lack the energy & raw materials to complete
process
Cellular Control over Mitosis
 Anchorage dependence
o Animal cells must be in contact with a solid surface to divide
 Density-dependent inhibition
o Crowded cells stop dividing
 Growth factors
o Required to start & continue dividing
o Secreted by other cells
Cell Cycle Checkpoints
Cell cycle has checkpoints:
 Structure of chromosomal DNA monitored
 Completion of phases monitored
 Determines if good time for cell division
 Rely on internal and external cues
 G1 checkpoint is the most important:
o If no go-ahead signal, cell will switch to non-dividing G0 phase
o E.g., nerve and muscle cells remain in Go indefinitely
Cancer and Cell Division
 If immune system doesn’t recognize and destroy a cancerous cell, it may divide
multiple times and form a tumor
o Benign: Cells remain localized
o Malignant: Spread to other parts of the body and disrupts function
Coordination of Cell Division
 A multicellular organism needs to coordinate cell division across different tissues
and organs
o Critical for normal growth, development and maintenance
 Coordinate timing of cell division
 Coordinate rates of cell division
 Not all cells can have the same cell cycle
Frequency of cell division
 Frequency of cell division varies by cell type
o Embryo
 Cell cycle < 20 minute
o Skin cells
 Divide frequently throughout life
 12-24 hours cycle
o Liver cells
 Retain ability to divide, but keep it in reserve
 Divide once every year or two
o Mature nerve cells and muscle cells
 Don’t divide at all after maturity
 Permanently in G0
Overview of Cell Cycle Control
 Two irreversible points in cell cycle
o Replication of genetic material
o Separation of sister chromatids
 Checkpoints:
o Process is assessed and possibly halted
o Cell cycle is controlled by STOP and GO chemical signals at critical points
o Signals indicate if key cellular processes have been completed correctly
 3 major checkpoints:
o G1/S
 can DNA synthesis begin?
o G2/M
 has DNA synthesis been completed correctly?
o commitment to mitosis
 spindle checkpoint
o are all chromosomes attached to spindle?
 can sister chromatids separate correctly?
 G1/S checkpoint
o Most critical checkpoint
 Primary decision point
 “restriction point”
 If cell receives “GO” signal, it divides
 Internal signals: cell growth (size), cell nutrition
 External signals: “growth factors”
 If cell does not receive signal, it exits cycle and switches to Go phase
 Non-dividing, working state
 G0 phase
o Non-dividing, differentiated state
o Most human cells in G0 phase
 Liver cells
 In G0, but can be “called back” to cell cycle by external cues
 Nerve and muscle cells
 Highly specialized
  Arrested in G0 and can never divide
Activation of cell division
 How do cells know when to divide?
o Cell communication signals
 Chemical signals in cytoplasm give cue
 Signals usually mean proteins
 Activators
 Inhibitors

“Go-ahead” signals
 Protein signals that promote cell growth & division
o internal signals
 “promoting factors”
o external signals
 “growth factors”
 Primary mechanism of control
o Phosphorylation
 kinase enzymes
 either activates or inactivates cell signals
Cell Cycle signals
 Cell cycle controls
o cyclins
 regulatory proteins
 levels cycle in the cell
 Cdk’s
o cyclin-dependent kinases
o phosphorylates cellular proteins
 activates or inactivates proteins
 Cdk-cyclin complex
o triggers passage through different stages of cell cycle
o Interaction of Cdk’s and different cyclins triggers the stages of the cell cycle
o There are multiple cyclins, each with a specific role. Cyclins are unstable.
Some are triggered for destruction by phosphorylation. Others are inherently
unstable and are synthesized discontinuously during the cell cycle.
o Oscillations in the activities of cyclin-dependent kinases (CDKs) dictate
orderly progression through the cell division cycle. In the simplest case of
yeast, a progressive rise in the activity of a single cyclin-CDK complex can
initiate DNA synthesis and then mitosis, and the subsequent fall in CDK
activity resets the system for the next cell cycle.
 o In most organisms, however, the cell cycle machinery relies on multiple
cyclin-CDKs, whose individual but coordinated activities are each thought to
be responsible for just a subset of cell cycle events

Cyclin and Cyclin-dependent kinases

 CDKs & cyclin drive cell from one phase to next in cell cycle
o proper regulation of cell cycle is so key to life that the genes for these
regulatory proteins have been highly conserved through
evolution
o the genes are basically the same in yeast, insects, plants & animals (including
humans)
 CDK and cyclin together form an enzyme that activates other proteins by chemical
modification (phosphorylation). The amount of CDK molecules is constant during the
cell cycle, but their activities vary because of the regulatory function of the cyclins.
CDK can be compared with an engine and cyclin with a gear box controlling whether
the engine will run in the idling state or drive the cell forward in the cell cycle.

External signals
 Growth factors
o coordination between cells
o protein signals released by body cells that stimulate other cells to divide
 density-dependent inhibition
 crowded cells stop dividing
 each cell binds a bit of growth factor
o not enough activator left to trigger division in any one
cell
 anchorage dependence
 to divide cells must be attached to a substrate
 o “touch sensor” receptors

Growth Factors and Cancer

 Growth factors can create cancers
o proto-oncogenes
 normal growth factor genes that become oncogenes (cancer-causing)
when mutated
 stimulates cell growth
 if switched “ON” can cause cancer
 example: RAS (activates cyclins)
o tumor-suppressor genes
 inhibits cell division
 if switched “OFF” can cause cancer
 example: p53
Cancer and Cell Growth
 Cancer is essentially a failure of cell division control
o unrestrained, uncontrolled cell growth
 What control is lost?
o lose checkpoint stops
o gene p53 plays a key role in G1/S restriction point
 p53 protein halts cell division if it detects damaged DNA
 options:
o stimulates repair enzymes to fix DNA
o forces cell into G0 resting stage
o keeps cell in G1 arrest
o causes apoptosis of damaged cell
o ALL cancers have to shut down p53 activity
P53 – master regulator gene
Development of Cancer
 Cancer develops only after a cell experiences ~6 key mutations (“hits”)
o unlimited growth
 turn on growth promoter genes
o ignore checkpoints
 turn off tumor suppressor genes (p53)
o escape apoptosis
 turn off suicide genes
o immortality = unlimited divisions
 turn on chromosome maintenance genes
o promotes blood vessel growth
 turn on blood vessel growth genes
o overcome anchor & density dependence
 turn off touch-sensor gene
What causes these “hits”?
 Mutations in cells can be triggered by
o UV radiation
o chemical exposure
o radiation exposure
o heat
o cigarette smoke
o pollution
o age
o genetics