The Cell Cycle Mitosis & Beyond…

THINK: Of how many cells are you composed? When an organism grows bigger do you get more cells or just bigger cells or both? When do your cells divide the fastest? Slowest? Do cells ever stop dividing? Are all cells capable of division and replacement?

Why does a cell divide? As a cell absorbs nutrients and gets larger, the volume of the cell increases faster than the surface area. -Therefore, the demands of the cell (the volume) exceed the ability of the cell to bring in nutrients and export wastes. Solution? Divide into two smaller cells

When is cell division occurring? GROWTH -increase number of cells REPAIR -replace lost cells due to injury, disease CANCER – Abnormally high rates of cell division due to mutation Different kinds of cells divide at different rates: E. coli – 20 minutes (What domain?) Yeast cell – 2 hours (What domain? What kingdom?) Amoeba – a few days (What domain? What kingdom?) Human embryo cell – 15-20 minutes Human adult cell – 8 hours to 100 days

Aging All cells die after a certain number of divisions (programmed cell death-”apoptosis”). At any given time some cells are dividing and some cells are dying. Childhood Cell division > cell death Adulthood Cell division = cell death Aging Cell division < cell death

Control of the Cell Cycle Cell proliferation

Interphase ~ 90% of the time. Ø   G1: Little new cell absorbs nutrients and grows larger. Does protein synthesis, its job. Ø   S phase: Synthesis of new DNA (DNA replication) for daughter cells in preparation for mitosis. Ø   G2: Cell continues to grow, do protein synthesis, do its job. Gets too large, needs to divide.

Chromosomes exist in 2 different states, before and after they replicate their DNA. Before replication, chromosomes have one chromatid. After replication, chromosomes have 2 sister chromatids, held together at the centromere. Each chromatid is one piece of DNA with its supporting proteins. Remember that diploid cells have two copies of each chromosome, one from each parent. These pairs of chromosomes are NOT attached together.

Structure of a eukaryotic chromosome unreplicated chromosome arm centromere

Prior to cell division: chromosomes (DNA) are replicated (duplicated) duplicated chromosome – attached at their centromeres – as long as attached, known as sister chromatids duplicated chromosome

daughter chromosomes sister chromatids

How long is one cell cycle. Depends. Eg. Skin cells every 24 hours How long is one cell cycle? Depends. Eg. Skin cells every 24 hours. Some bacteria every 2 hours. Some cells every 3 months. Nerve cells, never. Cancer cells very short. Programmed cell death: Each cell type will only do so many cell cycles then die. (Apoptosis)

MITOSIS Equal distribution of the 2 sets of DNA amongst the 2 daughter cells. 4 Stages: “PMAT” 1. Prophase 2. Metaphase 3. Anaphase 4. Telophase How the Cell Cycle Works Mitosis Animation Cell Cycle

What is Mitotic Cell Division? Division of somatic cells (body cells) (non reproductive cells) in eukaryotic organisms A single cell divides into two identical daughter cells (cellular reproduction) => Maintains chromosome ploidy of cell

Ploidy – refers to the number of pairs of chromosomes in cells haploid – one copy of each chromosome – designated as “n” diploid – two copies (= pair) of each chromosome – designated as “2n”

As a cell enters mitosis from interphase it has 2 complete sets of chromosomes because of replication in the S phase. Each set must be re-arranged and distributed into the 2 new daughter nuclei. This is mitosis.

Prophase…   -Chromatin condenses (coils) into chromosomes. Sister chromatids joined by centromere. -Nuclear membrane dissolves. -Centrioles divide and move to opposite poles forming spindle between them.

chromatin nucleolus nucleus centrioles condensing chromosomes

Metaphase -Centromeres lock on to spindle fibre -Sister chromatids line up on metaphase plate. -Centromeres lock on to spindle fibre

Anaphase -Centromeres divide. -Spindle fibres contract pulling sister chromatids apart to poles.

Telophase: -New nuclear membranes form around new nuclei Mitosis Movie

CYTO KINESIS – Cytoplasm splits into 2 cells. -Animal cells: Cleavage furrow forms from outside in. - Plant cells: Division/cell plate forms from inside out.  

Cell now returns to interphase Cell now returns to interphase . The chromosomes uncoil back into chromatin. The whole cell cycle starts over again….. http://www.cellsalive.com/mitosis.htm

At any point in time the cells in a tissue will be at different stages in the cell cycle.

Mitosis Stages Put these in the correct order..

The Guarantee of Mitosis… The 2 daughter cells formed are identical to each other and identical to the mother cell. Why is this so important?

In Mitosis, each daughter cell is exactly the same as the original mother cell. Cell Differentiation

Propogation of plants by cuttings Budding of Yeast Mitosis is also an ASEXUAL form of reproduction. These are other examples of the uses of mitosis to create new organisms asexually: Propogation of plants by cuttings Runners from plants like strawberries

Homologous pairs of chromosomes: Each chromosome has a certain gene sequence on it. Eg. Chrom #1 Has insulin, foot size, and lactase on it. You have a chromosome one from your mom and one from your dad. So you have 2 genes for each trait. One from your mom – one from your dad. A homologous pair is a pair with the same gene sequence – one from mom, one from dad.

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. They 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. Another control: normal cells are mortal. This means that they can divide about 50 times and then they lose the ability to 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. A third control: 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.

Many Mutations Lead to Cancer All cancer is genetic, in that it is triggered by altered genes. Genes that control the orderly replication of cells become damaged, allowing the cells to reproduce without restraint. Cancer usually arises in a single cell. The cell's progress from normal to malignant to metastatic appears to follow a series of distinct steps, each controlled by a different gene or set of genes.

Even though all cancer is genetic, just a small portion—perhaps 5–10% —is inherited. Most cancers come from random mutations that develop in body cells during one's lifetime—either as a mistake when cells are going through cell division or in response to injuries from environmental agents such as radiation or chemicals.

Cancer cells contain several (6-8) mutated genes Cancer cells contain several (6-8) mutated genes. These almost always include: mutations in genes that are involved in mitosis (oncogenes & tumor suppressor genes) Genes that regulate apoptosis Genes that maintain telomeres Genes that stimulate angiogenesis Metastasis genes Genetic Therapy & Breast Tumors

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.

Resources Mitosis  CANCER http://www.biology.iupui.edu/biocourses/N100H/ch8mitosis.html http://www.schoolscience.co.uk/content/4/biology/abpi/cancer/cancer3.html http://genetics.gsk.com/chromosomes.htm http://www.horton.ednet.ns.ca/staff/selig/handouts/bio12/cellrepro/cancermitosis.pdf#search=%22%22cancer%20animation%22%20mitosis%22 How Cancer grows http://www.pbs.org/wgbh/nova/cancer/grow_flash.html Mitosis: http://pages.csam.montclair.edu/~smalley/mitosis.mov http://faculty.pingry.org/thata/pingry_upload/movies/cellular_reproduction/plantcell_lily_mitosis.mov http://www.zo.utexas.edu/faculty/delozanne/celldivision/Mitosis%20Video.mov Cell Cycle & Cancer Animations: http://science.education.nih.gov/supplements/nih1/cancer/activities/activity2_animations.htm Cell Biology & Cancer Animations: http://www.learner.org/channel/courses/biology/units/cancer/images.html Mitosis & Meiosis Interactive Exercise: http://biologyinmotion.com/cell_division/ Mitosis Animations: http://www.sci.sdsu.edu/multimedia/mitosis/navigator.html Plant Cell Mitosis: http://www.teachersdomain.org/resource/tdc02.sci.life.stru.dnadivide/