The process of cell replication
Genes and Proteins Proteins do the work of the cell:
growth, maintenance, response to the environment, reproduction, etc.
Proteins are chains of amino acids. The sequence of amino acids in each protein is coded in the DNA as a specific sequence of A, C, G and T bases: a gene.
Each gene codes for a different protein.
Genes and Proteins Key points:
All cells within an organism have the same genes.
What makes cells different from each other is that different genes are turned on and turned off in different cells.
The DNA must be copied and then divided exactly so that each cell gets an identical copy.
MITOSIS VS. MEIOSIS Mitosis is normal cell division, which
goes on throughout life in all parts of the body. Meiosis is the special cell division that creates the sperm and eggs, the gametes. We will discuss meiosis separately.
Mitosis and meiosis occur in eukaryotes. Prokaryotes use a different method—”binary fission” to divide.
NUMBERS OF CHROMOSOMES
Humans have 46 chromosomes 23 from each parentEvery cell has the same 46
chromosomesEach species has a characteristic
number of chromosomes: ○ corn has 20, ○ house flies have 10, ○ chimpanzees have 48.
SOME VOCABULARY Chromosomes exist in 2 different
states: Chromatin: Between cell divisions,
DNA/protein complex is loosely coiled (easier for protein synthesis)
Chromatid: Right after DNA replication, the chromosomes are tightly coiled together (it is easier to “arrange” chromosomes this way) There are 2 copies of the
chromosome Centromere: The two copies of the
chromatid after replication are held together by the centromere.
CELL CYCLE Some cells divide constantly: cells in the
embryo, skin cells, gut lining cells, etc. Other cells divide rarely or never: only to replace themselves.
Actively dividing cells go through a cycle of events that results in mitosis. Most of the cycle was called “interphase” by the microscopists who first studied cell division. During interphase the cell increases in size, but the chromosomes are invisible.
The 3 stages of interphase are called G1, S, and G2.
INTERPHASE
Interphase is the normal part of cellular function. It includes the following (about 90% of cell life):G1 phaseS phaseG2 phase
prop
hase
met
aph
ase
anap
has
ete
loph
ase
cytokinesis
G2(Gap 2)
S-Phase(DNA Self-Replication)
M
1
2
G1(Gap 1)
G0THECELLCYCLE
http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells2.html
M I T O S I S
G1 (GAP 1) PHASE G1 (“Gap”) is the period between
mitosis and S, when each chromosome has 1 chromatin (not chromatid). Cells spend most of their time in G1: it is the time when the cell grows and performs its normal function. Control of cell division occurs in G1: a cell that isn’t destined to divide stays in G1, while a cell that is to divide enters the S phase.
S PHASE
The S phase (“Synthesis”) is the time when the DNA is replicated, when the chromosome goes from having one chromatin to having 2 chromatids held together at the centromere.
G2 (GAP 2) PHASE
G2 is the period between S and mitosis. The chromosome have 2 chromatids, and the cell is getting ready to divide.
HOW TO IDENTIFY INTERPHASE
Interphase
nuclear envelope
clearly visible
chromatin,NOchromosomes,yet
http://www.fed.cuhk.edu.hk/~johnson/photomicrographs/mitosis/animal/animal_interphase.htm
nucleolus (if any) still visible
INTERPHASE
http://iccbweb.med.harvard.edu/mitchisonlab/Pages/mt.html
interphaseinterphase
INTERPHASE
Allium root tip
Coregonus blastula
INTERPHASE is thenormal lifetime of acell, after being“born” by division,and before it dividesitself.
MITOSISINTERPHASE is nota stage of mitosis !
Biological Science, a Molecular Approach. BSCS Blue Version. Heath and Company, 1996.
What is MITOSIS ?
THE PROCESS BY WHICH TWO NEW NUCLEII ARE FORMED, WITH EXACTLY
THE SAME KIND AND NUMBER OF CHROMOSOMES AS THE PARENT CELL.
(1 CELL TO 2 CELLS)
http://fairmanstudios.com/als.htm
STEPS IN MITOSIS (In AP, the phases are not
emphasized) PROPHASE METAPHASE ANAPHASE TELOPHASE
PROPHASE In prophase, the cell begins the process of
division. The chromosomes condense. The
proteins attached to the DNA cause the chromosomes to go from long thin structures to short fat one, which makes them easier to pull apart (VISIBLE).
The nuclear envelope disappears. The double membrane that surround the nucleus dissolves into a collection of small vesicles, freeing the chromosomes to use the whole cell for division
Centrosomes form and move to opposite poles. During interphase, the pair of centrosomes were together just outside the nucleus. In prophase they separate and move to opposite ends of the cell.
The spindle starts to form, growing out of the centrosomes towards the chromosomes.
PROMETAPHASE
Nuclear membrane fragments Spindle interaction with chromosomes Kinetochore develops at the
centromere (this is where the spindle microtubules are going to bind)
HOW TO IDENTIFY PROPHASE
PROPHASE
•Nuclear membrane dissolves.•Nucleolus disappears.•Chromosomes form.•Centrioles migrate & form spindle.
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
PROPHASE
chromosomesbecome visible
nuclear envelopedisappears
nucleolusdisappears
http://www.ac-dijon.fr/pedago/svt/documents/mitose/prophase.gif
PROPHASE
http://www.itg.uiuc.edu/technology/atlas/structures/mitosis/prophase.htm
PROPHASE
Coregonus blastulaAllium root tip
METAPHASE Metaphase is a short
resting period where the chromosomes are lined up on the equator of the cell, with the centrosomes at opposite ends and the spindle fibers attached to the kinetochore. Everything is aligned for the rest of the division process to occur.
HOW TO IDENTIFY METAPHASE
METAPHASE
http://www.chembio.uoguelph.ca/educmat/chm736/cycletx.htm
•chromatids line up on the equator.
chromatids
spindle
centriole
METAPHASE
http://genenlab.spoono.com/gnu/mandm.shtml
TWO IDENTICAL COPIES OF ONE CHROMOSOME.
THISCHROMATIDWILL SOONMOVE TO
NORTH POLE
THISCHROMATIDWILL SOONMOVE TO
SOUTH POLE
Nature (408. 423, 2000).
chromatids spindle
centriole
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
METAPHASE
http://iccbweb.med.harvard.edu/mitchisonlab/Pages/mt.html
METAPHASE
Coregonus blastulaAllium root tip
ANAPHASE In anaphase, the
centromeres divide. At this point, each individual chromosome goes from: 1 chromosome with 2
chromatids to: 2 chromosomes with
one chromatid each. Then the spindle fibers
contract, and the chromosomes are pulled to opposite poles, towards the centrosomes.
HOW TO IDENTIFY ANAPHASE
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
ANAPHASE
•chromatids migrate to each pole.
ANAPHASE
http://www.univ-orleans.fr/SCIENCES/BIOCHIMIE/MMC/accueil.htm
Conly Rieder http://www.wadsworth.org/BMS/SCBlinks/WEB_MIT2/HOME.HTM
ANAPHASE
early late
ANAPHASE
Coregonus blastulaAllium root tip
TELOPHASE In telophase the cell actually
divides. The chromosomes are at the
poles of the spindle. The spindle disintegrates The nuclear envelope re-forms
around the two sets of chromosomes (become less coiled).
The cytoplasm is divided into 2 separate cells, the process of cytokinesis.
CYTOKINESIS The organelles (other than the
chromosomes) get divided up into the 2 daughter cells passively: they go with whichever cell they find themselves in.
Plant and animal cells divide the cytoplasm in different ways.
In plant cells, a new cell wall (CELL PLATE)made of cellulose forms between the 2 new nuclei, about where the chromosomes lined up in metaphase. Cell membranes form along the surfaces of this wall. When the new wall joins with the existing side wall, the 2 cells have become separate.
In animal cells, a ring of actin fibers (microfilaments are composed of actin) forms around the cell equator and contacts, pinching the cell in half. (CLEAVAGE FURROW)
CELL CYCLE CONTROL
These will control whether a cell divides or notGrowth Factor: a protein that is released that
induces a cell to divide (cell communication)Density-Dependent Inhibition: if an area is too
crowded with cells, cell division is inhibited. If the area lacks cells, division is allowed to occur
Anchorage Dependence: must be attached to a substrate
HOW TO IDENTIFY TELOPHASE
http
://w
ww
.bm
b.ps
u.ed
u/co
urse
s/bi
sci2
/mito
sis/
mito
sis.
htm
•Chromosomes dissolve.
•Nuclear membrane forms.•New nucleoli form.
•Mitotic spindle dissolves.
TELOPHASE
TELOPHASE
ONEDAUGHTERNUCLEUSFORMS AT
NORTH POLE
ONEDAUGHTERNUCLEUSFORMS AT
SOUTH POLESPINDLEAPPARATUSDISSOLVES
TELOPHASE
early late
New nuclei form at the poles. Cytokinesis
begins.
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
TELOPHASE
TELOPHASE
Coregonus blastulaAllium root tip
Summary of Mitosis Prophase:
○ Chromosomes condense○ Nuclear envelope disappears○ centrosomes move to opposite sides of the cell○ Spindle forms and attaches to centromeres on the chromosomes
Metaphase○ Chromosomes lined up on equator of spindle○ centrosomes at opposite ends of cell
Anaphase○ Centromeres divide: each 2-chromatid chromosome becomes two 1-chromatid
chromosomes○ Chromosomes pulled to opposite poles by the spindle
Telophase○ Chromosomes de-condense○ Nuclear envelope reappears○ Cytokinesis: the cytoplasm is divided into 2 cells
CYTOKINESIS
1 2
MITOSIS isaboutorganizing anddistributing
CHROMOSOMES
http://www.dartmouth.edu/artsci/bio/cbbc/courses/bio4/bio4-lectures/theCell.html
Cancer Cancer is a disease of uncontrolled cell division. It starts with a
single cell that loses its control mechanisms due to a genetic mutation. That cell starts dividing without limit, and eventually kills the host.
Normal cells are controlled by several factors. Normal cells stay in the G1 stage of the cell cycle until they
are given a specific signal to enter the S phase, in which the DNA replicates and the cell prepares for division. Cancer cells enter the S phase without waiting for a signal.
Normal cells are mortal. This means that they can divide about 50 times and then they lose the ability to divide, and eventually die. This “clock” gets re-set during the formation of the daughter cells. Cancer cells escape this process of mortality: they are immortal and can divide endlessly.
Normal cells that suffer significant chromosome damage destroy themselves due to the action of a gene called “p53”. Cancer cells either lose the p53 gene or ignore its message and fail to kill themselves.
Cancer Progression There are many different forms of cancer, affecting different cell
types and working in different ways. All start out with mutations in specific genes called “oncogenes”. The normal, unmutated versions of the oncogenes provide the control mechanisms for the cell. The mutations are caused by radiation, certain chemicals (carcinogens), and various random events during DNA replication.
Once a single cell starts growing uncontrollably, it forms a tumor, a small mass of cells. No further progress can occur unless the cancerous mass gets its own blood supply. “Angiogenesis” is the process of developing a system of small arteries and veins to supply the tumor. Most tumors don’t reach this stage.
A tumor with a blood supply will grow into a large mass. Eventually some of the cancer cells will break loose and move through the blood supply to other parts of the body, where they start to multiply. This process is called metastasis. It occurs because the tumor cells lose the proteins on their surface that hold them to other cells.
How is cancer harmful? What are the ways in which cancer is harmful? Some examples:
Lung cancer can damage the surrounding tissue and prevent the normal functioning of the lung until it collapses or fails
Stomach cancer can prevent the uptake of nutrients and cause loss of food uptake
Bone cancer can prevent the creation of blood cellsSome cancers create “chemcials” that can disrupt
the delicate balance of the bodySome cancers can lead to infections
Cancer Treatment Two basic treatments: surgery to remove the tumor, and
radiation or chemicals to kill actively dividing cells. It is hard to remove all the tumor cells. Tumors often lack
sharp boundaries for easy removal, and metastatic tumors can be very small and anywhere in the body.
Radiation and chemotherapy are aimed at killing actively dividing cells, but killing all dividing cells is lethal: you must make new blood cells, skin cells, etc. So treatment must be carefully balanced to avoid killing the patient.
Chemotherapy also has the problem of natural selection within the tumor. If any of the tumor cells are resistant to the chemical, they will survive and multiply. The cancer seems to have disappeared, but it comes back a few years later in a form that is resistant to chemotherapy. Using multiple drugs can decrease the risk of relapse: it’s hard for a cell to develop resistance to several drugs at the same time.
WHAT DO YOU THINK?
What do you think would be the OVERLYING purpose of cancer research?
What do you think are the major strategies to “cure” cancer?
DEXOSOMES
1. Create dendritic cells
2. Induce the production of dexosomes (activates immune system)
3. Load the dexosomes with a peptide (protein that is found on a marker for cancer cells . . . acts as an antigen)
4. The peptide loaded dexosomes activate your immune system to attack and destroy cancer cells.