Cytokinesis (cell division)

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Cytokinesis (cell division)
Today:
Chromosomes – information carriers
Cell division – daughter cells inherit a
chromosome complement identical to
that of the parent cell
Cancer - Things go terribly
wrong.......
A tightrope analogy: cells constantly respond and adapt to signals
from their environment
Positive and negative signals need to be balanced
Normal controls on the cell cycle are disrupted in cancer
From chromosomes to cancer....
•Chromosomes carry large numbers of genes
•Normal cells are euploid – they have the expected number of
chromosome sets in a karyotype (23 pairs of chromosomes in humans)
•Aneuploid cells have abnormal numbers of chromosomes. Very few
aneuploidies are viable, because gene products must be balanced for
proper cell function
Cancer cells are characterized by MANY mutations that disrupt the
balance in cells as well as chromosomal abnormalities
Few human trisomies are tolerated – may relate to the number of
genes that encode proteins
Human genome encodes ~21,000 proteins
Chromosome
Protein coding
genes
Incidence at
birth
% survival after
1 year
1
2102
0
0
13 (Pateau)
318
~1/15,000
<5%
18 (Edward)
268
~1/8000
<5%
21
225
~1/800
85%
22
431
very rare
0
X
815
viable
Y
45
viable
X chromosome is subject to special regulation (more later)
Chromosome (structural) mutations involve blocks of genes
Some are large enough to be detected on karyotypes
Exchanges can also occur between chromosomes
Translocations can have severe effects
Number of euploid gametes is reduced
The Human Genome Project has
revealed a surprising number of
small deletions and insertions on
every chromosome
We have probably underestimated human variation!
Cell Division
Daughter cells are identical copies of the parent cell
Mitosis (nuclear division) occupies a small
fraction of the eukaryotic cell cycle
Interphase includes S phase
and two gap (G1 and G2) phases
Chromosomes condense
and become visible during
mitosis
At the end of mitosis, two daughter cells will have the same chromosomes as
the parent
Fluorescent technique based on DNA hybridization “paints” each
chromosome a different color
Interphase
cell
Mitotic
chromosomes
Chromosomes decondense during interphase
A spindle provides the
machinery for pulling the
chromosomes apart
Theodor Boveri
mitotic spindle in an Ascaris egg
Boveri noted that the mitotic chromosomes split down their
middle before they moved to opposite poles during mitosis
Spindle has fibers made of microtubules that move
relative to another and change length during mitosis
spindle pole is the
nucleation center
for several sets of
microtubules
Motor proteins
provide the power
Prophase
Chromosomes condense
Nuclear membrane is intact
Spindle poles begin to organize
outside the nucleus
Prometaphase
Nuclear membrane breaks
down
Spindle fibers assemble
Metaphase
Spindle is fully assembled
Chromosomes line up at the equator
Fibers connect centromeres to
opposite poles
Force is equalized
Anaphase
Chromosomes break at
centromeres
Sister chromatids are drawn to
opposite poles
Telophase
Nuclear membrane reforms
Chromosomes decondense
Cytokinesis (cell division)
Contractile ring separates
daughter cells
Today we can watch mitosis in living cells and appreciate its precision
Mitosis explains the accuracy of genetic transmission
Mr. W’s Mitosis Rap
Cancer
A disease of somatic (non germline) mutations
Many mutations and chromosomal abnormalities are found in cancer
DNA sequencing is revealing the genes involved in cancer as well as the
heterogeneity in tumors
No two cancers are the same!!!
Cells normally receive a host of
signals from within and from
other cells that tell them when to
divide
Processing goes awry
during cancer
Are the chromosomes aligned
properly on the spindle?
Numerous checkpoints in
the cell cycle
Is the environment favorable
for division?
Is the DNA replicated
properly?
Is the DNA damaged?
Cells that don’t pass
checkpoints initiate a
suicide pathway
Is the environment
favorable? Nutrients?
Hormones? Stressors?
Is the DNA damaged?
Is the cell large enough?
Cells die by apoptosis – programmed cell death
(Greek: apo - from/off/without, ptosis - falling)
membrane pinches
off small fragments
that other cells will
ingest
fragmented
nuclei
apoptotic bodies in
cytoplasm are evidence
of self-digestion
Rapid and leaves no trace
In adult tissues, the rate of cell death is equal to the rate of cell death

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