Mitosis Cell Division E. McIntyre

In The Beginning One  Most of the organisms we see started out as one cell  Humans start out as a single cell, the zygote, formed by uniting a sperm and egg  The zygote divides to make approximately one trillion cells  During the process of dividing, cells become specialized to function in the various tissues and organs of the body  Mitosis is the process of cell division in eukaryotic cells

Why Cells Must Divide  In multi-celled organisms (like humans) cells specialize for specific functions thus the original cells must divide to produce different kinds of cells  Cells can only take in nutrients and excrete waste products over the surface of the membrane that surrounds them. The surface to volume ratio decreases with the square of the volume (unless special accommodations are made) 2 cm Surface 24 cm 2 / volume 8 cm 3 = 3 1 cm Surface 6 cm 2 / volume 1cm 3 = 6

The Cell Lifecycle  The cell lifecycle is well defined and can be divided into four stages: –Gap 1 (G1) - The growth phase in which most cells are found most of the time –Synthesis (S) - During which new DNA is synthesized –Gap 2 (G2) - The period during which no transcription or translation occurs and final preparations for division are made –Mitosis - Cell division

G1 M M G2 S S The Cell Life Cycle Gap 1 - Doubling of cell size. Regular cellular activities. transcription and translation etc. Synthesis of DNA - Regular cell activities cease and a copy of all nuclear DNA is made Gap 2 - Final preparation for division Mitosis - Cell division

Stages Of Mitosis  During mitosis an exact copy of the genetic material in the “mother” cell must be distributed to each “daughter” cell  Each stage of mitosis is designed to achieve equal and exact distribution of the genetic material which has been copied during the S phase of the cell cycle

Stages Of Mitosis  Interphase - The in between stage - Originally metaphase was thought to be a resting stage now we know that this is the stage most cells spend their time in doing the things that cells do and, if they are preparing to divide, growing and replicating their DNA G1 M M G2 S S Interphase

Stages Of Mitosis  Prophase - The beginning phase - DNA which was unraveled and spread all over the nucleus is condensed and packaged  Metaphase - Middle stage - Condensed chromosomes line up along the equator of the cell  Anaphase - One copy of each chromosome moves to each pole of the cell  Telophase - End stage - New nuclear membranes are formed around the chromosomes and cytokinesis (cytoplasm division) occurs resulting in two daughter cells

Stages Of Mitosis Interphase Anaphase Telophase Metaphase Mitotic spindle Prophase Nucleus with un-condensed chromosomes Equator of the cell Condensed chromosomes Disappearing nuclear membrane Poles of the cell Mother cell Two daughter cells

A T T A G C C G G C TATA T A G C C G G C T A A T Packaging DNA Histone proteins Histone octomer B DNA Helix 2 nm

A T T A G C C G G C TATA T A G C C G G C T A A T Packaging DNA Histone proteins B DNA Helix Histone octomer 2 nm

A T T A G C C G G C TATA T A G C C G G C T A A T Packaging DNA Histone proteins Histone octomer Nucleosome 11 nm B DNA Helix 2 nm

Packaging DNA A T T A G C C G G C T A A T

Packaging DNA A T T A G C C G G C T A A T

Packaging DNA A T T A G C C G G C T A A T Protein scaffold 11 nm “Beads on a string” 30 nm Tight helical fiber Looped Domains 200 nm

Packaging DNA G C A T Protein scaffold Metaphase Chromosome 700 nm 11 nm 30 nm 200 nm 2 nm Looped Domains Nucleosomes B DNA Helix Tight helical fiber

Replication Chromosomes, Chromatids and Centromeres Centromere Chromosome arm Identical chromatid Chromatid Anaphase A packaged chromosome Two identical chromosomes

Important Link to DNA Coiling 

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 gametes. 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.

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.