MitosisMitosisCell DivisionCell Division

E. McIntyreE. McIntyre

In The Beginning OneIn The Beginning One Most of the organisms we see started out as one cellMost of the organisms we see started out as one cell Humans start out as a single cell, the zygote, formed Humans start out as a single cell, the zygote, formed

by uniting a sperm and eggby uniting a sperm and egg The zygote divides to make approximately one trillion The zygote divides to make approximately one trillion

cellscells During the process of dividing, cells become During the process of dividing, cells become

specialized to function in the various tissues and specialized to function in the various tissues and organs of the bodyorgans of the body

Mitosis is the process of cell division in eukaryotic Mitosis is the process of cell division in eukaryotic cellscells

Why Cells Must DivideWhy Cells Must Divide In multi-celled organisms (like humans) cells In multi-celled organisms (like humans) cells

specialize for specific functions thus the original specialize for specific functions thus the original cells must divide to produce different kinds of cells must divide to produce different kinds of cellscells

Cells can only take in nutrients and excrete Cells can only take in nutrients and excrete waste products over the surface of the waste products over the surface of the membrane that surrounds them. The surface to membrane that surrounds them. The surface to volume ratio decreases with the square of the volume ratio decreases with the square of the volume (unless special accommodations are volume (unless special accommodations are made)made)

2 cmSurface 24 cm2/volume 8 cm3 = 3

1 cm

Surface 6 cm2/volume 1cm3= 6

The Cell LifecycleThe Cell Lifecycle The cell lifecycle is well defined and can be The cell lifecycle is well defined and can be

divided into four stages:divided into four stages:– Gap 1Gap 1 (G1) - The growth phase in which most cells (G1) - The growth phase in which most cells

are found most of the timeare found most of the time– SynthesisSynthesis (S) - During which new DNA is (S) - During which new DNA is

synthesizedsynthesized– Gap 2Gap 2 (G2) - The period during which no (G2) - The period during which no

transcription or translation occurs and final transcription or translation occurs and final preparations for division are madepreparations for division are made

– MitosisMitosis - Cell division - Cell division

G1G1

MM

G2G2

SS

The Cell Life CycleThe Cell Life CycleGap 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 MitosisStages Of Mitosis During mitosis an exact copy of the During mitosis an exact copy of the

genetic material in the “mother” cell must genetic material in the “mother” cell must be distributed to each “daughter” cellbe distributed to each “daughter” cell

Each stage of mitosis is designed to Each stage of mitosis is designed to achieve equal and exact distribution of achieve equal and exact distribution of the genetic material which has been the genetic material which has been copied during the S phase of the cell copied during the S phase of the cell cyclecycle

Stages Of MitosisStages Of Mitosis Interphase -Interphase - The in between stage - The in between stage -

Originally metaphase was thought to be a Originally metaphase was thought to be a resting stage now we know that this is the resting stage now we know that this is the stage most cells spend their time in doing the stage most cells spend their time in doing the things that cells do and, if they are preparing things that cells do and, if they are preparing to divide, growing and replicating their DNAto divide, growing and replicating their DNA

G1G1

MM

G2G2

SS

Interphase

Stages Of MitosisStages Of Mitosis Prophase -Prophase - The beginning phase - DNA which was The beginning phase - DNA which was

unraveled and spread all over the nucleus is unraveled and spread all over the nucleus is condensed and packagedcondensed and packaged

Metaphase -Metaphase - Middle stage - Condensed Middle stage - Condensed chromosomes line up along the equator of the cellchromosomes line up along the equator of the cell

Anaphase -Anaphase - One copy of each chromosome One copy of each chromosome moves to each pole of the cellmoves to each pole of the cell

Telophase -Telophase - End stage - New nuclear membranes End stage - New nuclear membranes are formed around the chromosomes and are formed around the chromosomes and cytokinesis (cytoplasm division) occurs resulting in cytokinesis (cytoplasm division) occurs resulting in two daughter cellstwo daughter cells

Stages Of MitosisStages 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 TT AG CC

G

G C

TA

T

AG

C

C G

G C

T A

A T

Packaging DNAPackaging DNA

Histone proteins

Histoneoctomer

B DNA Helix 2 nm

A TT AG CC

G

G C

TA

T

AG

C

C G

G C

T A

A T

Packaging DNAPackaging DNA

Histone proteins

B DNA Helix

Histoneoctomer

2 nm

A TT AG CC

G

G C

TA

T

AG

C

C G

G C

T A

A T

Packaging DNAPackaging DNA

Histone proteins

Histoneoctomer

Nucleosome

11 nm

B DNA Helix 2 nm

Packaging DNAPackaging DNA

A TT AC G

C G

G C

T A

A T

Packaging DNAPackaging DNA

A TT AC G

C G

G C

T A

A T

Packaging DNAPackaging DNA

A TT AC G

C G

G C

T A

A T

Protein scaffold

11 nm“Beads on a string”

30 nm

Tight helical fiber

Looped Domains200 nm

Packaging DNAPackaging DNA

G

C

A

T

Protein scaffold

Metaphase Chromosome

700 nm

11 nm

30 nm200 nm

2 nm

Looped Domains

Nucleosomes

B DNA Helix

Tight helical fiber

Replication

Chromosomes, Chromatids Chromosomes, Chromatids and Centromeresand Centromeres

Centromere

Chromosome arm

Chromosome arm

Identicalchromatid

Chromatid

Anaphase

A packaged chromosome

Two identical chromosomes

Important Link to DNA CoilingImportant Link to DNA Coiling

http://www.biostudio.com/demo_freeman_dna_coiling.htmhttp://www.biostudio.com/demo_freeman_dna_coiling.htm

CancerCancer

•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 ProgressionCancer ProgressionThere 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 TreatmentCancer TreatmentTwo 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.