The cell cycle

1
The cell cycle prokaryotic eukaryotic Control
of the cell cycle loss of control- cancer What
is cell differentiation and why does it
happen? what is a stem cell? What is
cloning? implications of cloning
2
Cell division prokaryotes- binary fission one
bacterium divides into two one circular
chromosome replicates beforehand two
identical daughter cells form can take as
little as 15 minutes eukaryotes DNA is
replicated before cell division somatic cells-
mitosis two identical daughter cells germ
cells- meiosis gametes (sperm and eggs)
which fuse to form a zygote takes much
longer
3
(No Transcript)
4
Eukaryotic cells have several chromosomes Number
varies among species (p. 138) humans have 46 (23
pairs) diploid organisms have pairs
of chromosomes chromosome structure is
complex How much of that chromosome actually
contains genetic information?
5
(No Transcript)
6
(No Transcript)
7
How long does the cell cycle last? Depends on
the cell stem cells, embryonic cells- a few
hours (embryonic cells dont really have G1
and G2- why?) Some cells divide very
slowly Some cells divide when induced liver lym
phocytes
8
Cell division Cells grow during interphase DNA
is replicated during S phase Division of nucleus
during M phase (mitosis) Division of cytoplasm
(cytokinesis) Programmed cell death
(apoptosis) Cells divide only a certain number
of times and then die (Hayflick limit) Role of
telomeres?
9
Control of cell cycle- by 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
10
Early 1970s
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
11
I. G1 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
12
Many growth factors have been described how do
they 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
13
II. 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
14
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
must be phosphorylated Cyclin and Cdk must be
bound together to be active
15
Initial cyclin-Cdk complex is inactive a series
of phosphorylation and dephos- phorylation steps
make it active Complex is called MPF
(mitosis-promoting factor) Present in both
mitosis and meiosis highly conserved
16
MPF activates a complex that degrades cyclin
17
G1 checkpoints 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 p53 prevents damaged from
dividing (by inhibiting Rb pathway) Abnormalitie
s in both genes are associated with hereditary
forms of cancer
18
III. Spindle assembly checkpoint,
between metaphase and anaphase Cell cycle can
be arrested if spindle fibers are not attached
properly to chromatids
19
(No Transcript)
20
Cell growth is usually tightly regulated 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
21
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
22
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
23
If mutations occur in control genes, they
cant 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!)
24
(No Transcript)
25
What about this 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?
26
(No Transcript)
27
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, youre halfway
there! Mutations occur over time- cancer is more
common in older people Most cancer is NOT
inherited environmental damage causes most
cancer
28
What sorts of things cause this
damage? Radiation Toxins Chemicals Our bodies
have many processes that repair damaged DNA
29
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)
30
As more is known about mechanisms
of uncontrolled cell growth, new
treatment strategies will emerge Radiation Chemo
therapy Immunotherapy Kinase inhibitors Angiogenes
is inhibitors Gene replacement