Transcript cell cycle - APBiologyWiki

How long does the cell cycle last?
Depends on the cell
stem cells, embryonic cells- a few hours
Some cells divide very slowly
Some cells divide when induced
liver
lymphocytes
Some cells don’t divide
nerve cells
What controls the cell cycle?
Cell division
Interphase : Cell growth (G1 and G2)
S Phase : DNA is replicated
M phase : Division of nucleus (mitosis)
Cytokinesis: Division of cytoplasm
Apoptosis: Programmed cell death
Cells divide only a certain number of times
and then die (Hayflick limit)
Role of telomeres?
Control of cell cycle
special proteins and
enzymes that act as switches
G1 checkpoint- stop, pause or go into S phase
some cells stop permanently
G2 checkpoint- will cell divide?
M checkpoint- formation of new cells
Early 1970s: Experiments with Cell Fusion
M phase drives G1 cell into mitosis, even though
S phase has not occurred
S + G1: G1 cell starts S phase
S phase + G2: G2 will not undergo DNA synthesis
G1 checkpoint
Varies the most among cell types
First of several checkpoints is seen
What determines whether a cell
will grow?
Single-celled organisms grow if enough
nutrients
are present
Multicellular organisms must grow in a
controlled
way: growth factors
Mitogens stimulate cells to go into S phase
How do growth factors work?
Bind to tyrosine kinase receptors
Activate Ras pathway (a small membrane G
protein)

Cascade of phosphorylation reactions, followed
by transcription
Cell passes into S phase
G2 checkpoint (between G2 and M)
DNA synthesis must be complete and correct
Cell may be arrested at this point
This checkpoint tends to be more important
in certain types of cells, e.g., fertilized
frog eggs and certain strains of yeast
Cyclin-dependent kinases (Cdk)
First discovered in yeast
Different kinds of cyclins; levels oscillate at
different stages of cycle
Control mechanisms
availability of cyclins varies
Cdk (cyclin dependent kinases)
must be phosphorylated
Cyclin and Cdk must be bound together to be
active
Initial cyclin-Cdk complex is inactive
a series of phosphorylation and dephosphorylation steps make it active
Complex is called MPF (mitosis-promoting
factor)
Present in both mitosis and meiosis
Highly conserved
MPF activates a
complex that
degrades cyclin
Spindle assembly checkpoint
Between metaphase and anaphase
Cell cycle can be arrested if spindle fibers are
not attached properly to chromatids
Genes controlling G1 checkpoints
1. Rb prevents cell moving into S phase by binding
to a transcription factor
When Rb is phoshporylated it cannot bind so
cell can move into S phase
2. p53 prevents damaged cells from dividing
(by inhibiting Rb pathway)
Abnormalities in both genes are associated with
hereditary forms of cancer
Regulation of Cell Growth
Controls:
contact inhibition- cells will grow to a
certain density
finite number of cell divisions
“gatekeeper genes”
proto-oncogenes- stimulate growth
some make growth factors
some respond to growth factors
Types of proto-oncogenes
Growth factors
Receptors (G protein and tyrosine kinase)
Kinases
Transcription factors
Cdk-kinases
Mutant forms, oncogenes that promote cancer,
have been identified in every category
Tumor suppressors- inhibit cell growth
Cancers occur
•
when cells grow out of control
•
invade and damage tissues
•
cells themselves may not function
properly
How does this happen? Mutations accumulate
in DNA
If mutations occur in control genes, they can’t
regulate cell growth
Some defects in particular genes are associated
with specific cancers
BRCA-1 tumor suppressor gene associated with
some inherited breast cancers
p53- tumor suppressor- associated with many
colon, bladder, breast, brain, lung cancers
(about half of all cancers!)
Apoptosis – Cell Destruction
Damaged cell undergoes apoptosis
(programmed cell death)
Genetically regulated- cell has genes that both
promote and inhibit death
How does programmed cell death differ from
death by injury?
Inheritance of “cancer gene”:
Each cell has 2 copies of p53. If both become
damaged, they lose control of cell growth
If you inherit one “damaged” copy, you’re
halfway there!
Mutations occur over time- cancer is more
common in older people
Most cancer is NOT inherited; environmental
damage causes most cancer
What sorts of things cause this damage?
Radiation
Toxins
Chemicals
Our bodies have many processes that repair
damaged DNA
Avoid sun exposure
Avoid smoking
Eat moderately; consume fiber. Some foods
may help prevent cancer?
Early detection (especially important if you
have a family history of cancer)