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 parent Every cell has the same 46 chromosomes Each 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 phase S phase G2 phase

prophase metaphase anaphase telophase cytokinesis G2 (Gap 2) S-Phase (DNA Self- Replication) M 1 2 G1 (Gap 1) G0 THE CELL CYCLE 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, NO chromosomes, yet nucleolus (if any) still visible

INTERPHASE

interphase

INTERPHASE Allium root tip Coregonus blastula

INTERPHASE is the normal lifetime of a cell, after being “born” by division, and before it divides itself. MITOSIS INTERPHASE is not a 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)

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.

PROPHASE chromosomes become visible nuclear envelope disappears nucleolus disappears

PROPHASE

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 chromatids line up on the equator. chromatids spindle centriole

METAPHASE TWO IDENTICAL COPIES OF ONE CHROMOSOME. THIS CHROMATID WILL SOON MOVE TO NORTH POLE THIS CHROMATID WILL SOON MOVE TO SOUTH POLE

Nature ( , 2000). chromatids spindle centriole

METAPHASE

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

ANAPHASE chromatids migrate to each pole.

ANAPHASE

Conly Rieder ANAPHASE earlylate

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 not Growth 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

Chromosomes dissolve. Nuclear membrane forms. New nucleoli form. Mitotic spindle dissolves. TELOPHASE

ONE DAUGHTER NUCLEUS FORMS AT NORTH POLE ONE DAUGHTER NUCLEUS FORMS AT SOUTH POLE SPINDLE APPARATUS DISSOLVES

TELOPHASE early late New nuclei form at the poles. Cytokinesis begins.

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 12 MITOSIS is about organizing and distributing CHROMOSOMES

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 cells Some cancers create “chemcials” that can disrupt the delicate balance of the body Some 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.