ciclo celular
TRANSCRIPT
Overview: The Key Roles of Cell Division
• The ability of organisms to reproduce best
distinguishes living things from non-living matter
• The continuity of life is based upon the
reproduction of cells, or cell division
• Cell division is integral part of cell cycle• Cell division is integral part of cell cycle
Types of cell division
• Prokaryotes
– Binary fission
• Eukaryotes
– Mitosis:
• Growth, development & repair
• Asexual reproduction (yields genetically identical cells)
• Occurs in somatic (body) cells• Occurs in somatic (body) cells
– Meiosis:
• Sexual reproduction (yields genetically different cells with half the
# of chromosomes)
• Occurs in specific reproductive cells
• Yields gametes (e.g., eggs & sperm) or spores
• Eukaryotic cell division consists of:
– Mitosis, the division of the nucleus
– Cytokinesis, the division of the cytoplasm
Mitotic cell division results in genetically
identical daughter cells
• Cells duplicate their genetic material before they divide, ensuring that
each daughter cell receives an exact copy of the genetic material, DNA
• A dividing cell duplicates its DNA, allocates the two copies to opposite
ends of the cell, and only then splits into daughter cells
• Every eukaryotic species has a characteristic number of chromosomes
in each cell nucleusin each cell nucleus
• Somatic (non-reproductive) cells (normally) have two sets of
chromosomes
• Gametes (reproductive cells: sperm and eggs) (and spores) have half
as many chromosomes as somatic cells
• Eukaryotic chromosomes consist of chromatin, a complex of DNA and
protein that condenses during cell division
DNA associates with special proteins to form more stable structure called chromosomes (different
proteins in prokaryotes and eukaryotes, so chromosomes built different)
Chromosomes are found inside nucleus in eukaryotes
Human - 46 chromosomes, 23 pairs (1 set of 23 from egg, 1 set of 23 from sperm)
Each chromosome contains many genes
Gene is a segment of DNA that is responsible for controlling a trait (e.g., coding for a specific protein)
You can see stained chromosomes and these can be arranged in pairs. The picture of
arranged chromosomes is called a karyotype. Chromosomes are characterized by:
Length, position of the centromere, banding pattern
M
Mitosis
G1
Gap 1
G0
Resting
G2
Gap 2
S
Synthesis
• Cell has a “life cycle”
cell is formed from
a mitotic division
Cell cycle
cell grows & matures
to divide again
cell grows & matures
to never divide again
G1, S, G2, M G0
epithelial cells,
blood cells,
stem cells
brain nerve cells
liver cells
External signals
• Growth factors
– coordination between cells
– 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
» not enough activator left to trigger
division in any one cell
• anchorage dependence
– to divide cells must be attached to a
substrate
» “touch sensor” receptors
nuclear membrane
growth factor
nuclear pore
Growth factor signals
E2F
nucleuscytoplasm
cell division
nuclear membrane
protein kinasecascade chromosome
Cdkcell surfacereceptor
P
P
P
P
P
• Frequency of cell division varies by cell type
– embryo• cell cycle < 20 minute
– skin cells• divide frequently throughout life
• 12-24 hours cycle
Frequency of cell division
G2
S G1
M
metaphaseprophase
anaphasetelophase
interphase (G1, S, G2 phases)
mitosis (M)
cytokinesis (C)
C
• 12-24 hours cycle
– liver cells• retain ability to divide, but keep it in reserve
• divide once every year or two
– mature nerve cells & muscle cells• do not divide at all after maturity
• permanently in G0
Prophase
Metaphase
The The
Stages of Stages of
MMitosisitosis
Interphase
Anaphase Telophase
Mitosis in animal cells
The Cell Cycle Control System
• The sequential events of the cell cycle are directed by a
distinct cell cycle control system, which is similar to a clock
• The clock has specific checkpoints where the cell cycle
stops until a go-ahead signal is received
• For many cells, the G1 checkpoint seems to be the most • For many cells, the G1 checkpoint seems to be the most
important one
G1 checkpoint
G1
SControl
system
M
M checkpoint
G2 checkpoint
G2
G1 checkpoint
G0
G1 G1
If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.
If a cell does not receive a go-ahead signal at the G1
checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.
Cyclin-dependent protein kinases drive
progression through the cell cycle
• Cyclin-dependent kinases
(Cdks) are inactive unless
bound to cyclins
• Active complex
phosphorylates downstream
targets
• Cyclin helps to direct Cdks to
the target proteins
Cyclin Levels
Checkpoint: DNA damage arrests
the cell cycle in G1
Apoptosis
• Programmed cell death, cell suicide
• Pathway should be activated if “something goes wrong”– Especially involving DNA/chromosome damage
• Involves proteases called caspases
• Regulated by Bcl2 and BAX– BAX homodimer promotes apoptosis, Bcl2 homodimer blocks
apoptosis
– Some cancer cells overproduce Bcl2 and are resistant to some chemotherapies and radiation treatment
• Proteins involved in cell cycle checkpoints regulate pathway
DNA damage is causedby heat, radiation, or
p53 allows cellswith repairedDNA to divide.
Step 1 Step 3p53 triggers the destruction of cells damaged beyond repair.
NORMAL p53
Cell division stops, and p53 triggers enzymes to
Step 2
DNA repair enzymep53protein
p53protein
p53 — master regulator gene
by heat, radiation, or chemicals.
DNA damage iscaused by heat,radiation, or chemicals.
Step 1 Step 2
Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.
of cells damaged beyond repair.
ABNORMAL p53
abnormalp53 protein
cancercell
Step 3The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.
p53 triggers enzymes to repair damaged region.
The Morphology of Apoptosis
ApoptosisA genetically controlled cell suicide pathway
Programmed cell death, is a highly regulated process that allows a cell to
self-degrade in order for the body to eliminate unwanted or dysfunctional cells.
Cytoplasm shrinks
Chromosomes condense and fragment
Nuclear membrane breaks down
Apoptotic body formation
Engulfment of the cell corpse
Apoptosis
Growth Factors and Cancer
• Growth factors influence cell cycle
– proto-oncogenes
• normal genes that become oncogenes (cancer-
causing) when mutated
• stimulates cell growth• stimulates cell growth
• if switched on can cause cancer
• example: RAS (activates cyclins)
– tumor-suppressor genes
• inhibits cell division
• if switched off can cause cancer
• example: p53
M
Mitosis
G1
Gap 1
G0
Resting
G2
Gap 2
S
Synthesis
Cancer & Cell Growth
• Cancer is essentially a failure
of cell division control
– unrestrained, uncontrolled cell growth
• What control is lost?
– checkpoint stops– checkpoint stops
– gene p53 plays a key role in G1 checkpoint
• p53 protein halts cell division if it detects damaged DNA
– stimulates repair enzymes to fix DNA
– forces cell into G0 resting stage
– keeps cell in G1 arrest
– causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity
p53 discovered at Stony Brook by Dr. Arnold Levine
Development of Cancer
• Cancer develops only after a cell experiences ~6 key mutations (“hits”)
– unlimited growth • turn on growth promoter genes
– ignore checkpoints• turn off tumor suppressor genes
– escape apoptosis– escape apoptosis• turn off suicide genes
– immortality = unlimited divisions• turn on chromosome maintenance genes
– promotes blood vessel growth• turn on blood vessel growth genes
– overcome anchor & density dependence• turn off touch censor gene
Signaling pathways are linked into Networks!
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