Cellular biochemistryUnit 3

Cell cycle and Cancer

B.Sc Biochemistry II

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Cell DivisionAll cells are derived from pre-

existing cellsNew cells are produced for growth

and to replace damaged or old cellsDiffers in prokaryotes (bacteria) and

eukaryotes (protists, fungi, plants, & animals)

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Keeping Cells Identical

The instructions for making cell parts are encoded in the DNA, so each new cell must get a complete set of the DNA molecules

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DNA ReplicationDNA must be copied or

replicated before cell division

Each new cell will then have an identical copy of the DNA

Original DNA strand

Two new, identical DNA strands

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Identical Daughter Cells

Parent Cell

Two identical daughter cells

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Prokaryotic Chromosome

The DNA of prokaryotes (bacteria) is one, circular chromosome attached to the inside of the cell membrane

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Eukaryotic Chromosomes

All eukaryotic cells store genetic information in chromosomes

Most eukaryotes have between 10 and 50 chromosomes in their body cells

Human body cells have 46 chromosomes or 23 identical pairs

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Compacting DNA into Chromosomes

DNA is tightly coiled around proteins called histones

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Chromosomes in Dividing Cells

Duplicated chromosomes are called chromatids & are held together by the centromere

Called Sister Chromatids

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KaryotypeA picture of the

chromosomes from a human cell arranged in pairs by size

First 22 pairs are called autosomes

Last pair are the sex chromosomes

XX female or XY male

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Cell Reproduction

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Types of Cell Reproduction Asexual reproduction involves a single cell dividing to

make 2 new, identical daughter cells Mitosis & binary fission are examples of asexual

reproduction Sexual reproduction involves two cells (egg & sperm)

joining to make a new cell (zygote) that is NOT identical to the original cells

Meiosis is an example

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Cell Division in Prokaryotes Prokaryotes such as

bacteria divide into 2 identical cells by the process of binary fission

Single chromosome makes a copy of itself

Cell wall forms between the chromosomes dividing the cell

Parent cell

2 identical daughter cells

Chromosome doubles

Cell splits

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The Cell Cycle

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Five Phases of the Cell CycleG1 - primary growth phaseS – synthesis; DNA replicatedG2 - secondary growth phase

collectively these 3 stages are called interphase

M - mitosisC - cytokinesis

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Interphase - G1 Stage1st growth stage after cell divisionCells mature by making more

cytoplasm & organellesCell carries on its normal

metabolic activities

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Interphase – S StageSynthesis stageDNA is copied or replicated

Two identical copies of DNA

Original DNA

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Interphase – G2 Stage2nd Growth StageOccurs after DNA has been copiedAll cell structures needed for division are

made (e.g. centrioles)Both organelles & proteins are synthesized

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Mitosis

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Mitosis Division of the nucleus Also called karyokinesis Only occurs in eukaryotes Has four stages Doesn’t occur in some cells

such as brain cells

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Early ProphaseChromatin in nucleus condenses to form visible

chromosomesMitotic spindle forms from fibers in cytoskeleton

or centrioles (animal)

Chromosomes

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Late ProphaseNuclear membrane & nucleolus are broken

downChromosomes continue condensing & are

clearly visibleSpindle fibers called kinetochores attach to the

centromere of each chromosomeSpindle finishes forming between the poles of

the cell

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Review of Prophase

What the cell looks like

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Spindle Fibers The mitotic spindle form from the microtubules in

plants and centrioles in animal cells Polar fibers extend from one pole of the cell to the

opposite pole Kinetochore fibers extend from the pole to the

centromere of the chromosome to which they attach Asters are short fibers radiating from centrioles

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MetaphaseChromosomes, attached to the kinetochore

fibers, move to the center of the cellChromosomes are now lined up at the equator

Pole of the Cell

Equator of Cell

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Review of Metaphase

What the cell looks like

What’s occurring

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AnaphaseOccurs rapidlySister chromatids are

pulled apart to opposite poles of the cell by kinetochore fibers

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Anaphase Review

What the cell looks like

What’s occurring 11

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TelophaseSister chromatids at opposite polesSpindle disassemblesNuclear envelope forms around each set of

sister chromatidsNucleolus reappearsCYTOKINESIS occursChromosomes reappear as chromatin

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Comparison of Anaphase & Telophase

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CytokinesisMeans division of the cytoplasmDivision of cell into two, identical halves

called daughter cellsIn plant cells, cell plate forms at the equator

to divide cellIn animal cells, cleavage furrow forms to

split cell

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Daughter Cells of MitosisHave the same number of chromosomes as

each other and as the parent cell from which they were formed

Identical to each other, but smaller than parent cell

Must grow in size to become mature cells (G1 of Interphase)

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Eukaryotic Cell Division

Used for growth and repair Produce two new cells

identical to the original cell Cells are diploid (2n)

Chromosomes during Metaphase of mitosis

Prophase Metaphase Anaphase Telophase Cytokinesis

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Mitosis Animation

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Uncontrolled Mitosis If mitosis is not controlled,

unlimited cell division occurs causing cancerous tumors

Oncogenes are special proteins that increase the chance that a normal cell develops into a tumor cell

Cancer cells

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MeiosisFormation of Gametes

(Eggs & Sperm)

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Facts About MeiosisPreceded by interphase which includes

chromosome replicationTwo meiotic divisions --- Meiosis I and Meiosis IICalled Reduction- divisionOriginal cell is diploid (2n)Four daughter cells produced that are

monoploid (1n)

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Facts About MeiosisDaughter cells contain half the number of

chromosomes as the original cellProduces gametes (eggs & sperm)Occurs in the testes in males

(Spermatogenesis)Occurs in the ovaries in females (Oogenesis)

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Start with 46 double stranded chromosomes (2n)After 1 division - 23 double stranded chromosomes (n)After 2nd division - 23 single stranded chromosomes (n)  Occurs in our germ cells that produce gametes

More Meiosis Facts

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Why Do we Need Meiosis? It is the fundamental basis of sexual

reproductionTwo haploid (1n) gametes are brought

together through fertilization to form a diploid (2n) zygote

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Replication of Chromosomes Replication is the process

of duplicating a chromosome

Occurs prior to division Replicated copies are

called sister chromatids Held together at

centromere

Occurs in Interphase

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A Replicated Chromosome

Homologs (same genes, different alleles)

SisterChromatids(same genes,same alleles)

Gene X

Homologs separate in meiosis I and therefore different alleles separate.

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Meiosis Forms Haploid GametesMeiosis must reduce the chromosome number by

halfFertilization then restores the 2n number

from mom from dad child

meiosis reducesgenetic content

toomuch!

The right number!

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Meiosis: Two Part Cell Division

Homologsseparate

Sister chromatidsseparate

Diploid

Meiosis I

MeiosisII

Diploid

Haploid

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Meiosis I: Reduction Division

Nucleus Spindlefibers

Nuclearenvelope

Early Prophase I(Chromosome number doubled)

Late Prophase I

Metaphase IAnaphase I Telophase I

(diploid)

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Prophase I

Early prophaseHomologs pair.Crossing over occurs.

Late prophaseChromosomes condense.Spindle forms.Nuclear envelope fragments.

• Prophase I• It is the longest phase of meiosis. During prophase I, DNA is

exchanged between homologous chromosomes in a process called homologous recombination. This often results in chromosomal crossover. The new combinations of DNA created during crossover are a significant source of genetic variation, and may result in beneficial new combinations of alleles. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatics, with one chromosome coming from each parent. The process of pairing the homologous chromosomes is called synapses. At this stage, non-sister chromatids may cross-over at points called chiasmata

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Tetrads Form in Prophase IHomologous chromosomes(each with sister chromatids)   Join to form a TETRAD

Called Synapsis

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Crossing-Over Homologous

chromosomes in a tetrad cross over each other

Pieces of chromosomes or genes are exchanged

Produces Genetic recombination in the offspring

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Metaphase I

Homologous pairs of chromosomes align along the equator of the cell

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Anaphase I

Homologs separate and move to opposite poles.

Sister chromatids remain attached at their centromeres.

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Telophase I

Nuclear envelopes reassemble.

Spindle disappears.

Cytokinesis divides cell into two.

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Meiosis II

Only one homolog of each chromosome is present in the cell.

Meiosis II produces gametes with one copy of each chromosome and thus one copy of each gene.

Sister chromatids carry identical genetic information.

Gene X

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Meiosis II: Reducing Chromosome Number

Prophase IIMetaphase II

Anaphase IITelophase II

4 Identical haploid cells

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Prophase II

Nuclear envelope fragments.

Spindle forms.

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Metaphase II

Chromosomes align along equator of cell.

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Anaphase II

Sister chromatids separate and move to opposite poles.

Equator

Pole

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Telophase IINuclear envelope assembles.

Chromosomes decondense.

Spindle disappears.

Cytokinesis divides cell into two.

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Results of Meiosis

Gametes (egg & sperm) form

Four haploid cells with one copy of each chromosome

One allele of each gene

Different combinations of alleles for different genes along the chromosome

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Comparing Mitosis and

Meiosis

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Mitosis Meiosis

Number of divisions 1

2

Number of daughter cells

2 4

Genetically identical? Yes No

Chromosome # Same as parent Half of parent

Where Somatic cells Germ cells

When Throughout life At sexual maturity

Role Growth and repair Sexual reproduction

Comparison of Divisions

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Cell cycle regulation and Cancer

Cell cycle regulation

• The timing and rates of cell division in different parts of an animal or plant are Crucial for normal growth, development, and maintenance.

• The frequency of cell division varies with cell type.• Some human cells divide frequently throughout life (skin

cells), others have the ability to divide, but keep it in reserve (liver cells), and mature nerve and muscle cells do not appear to divide at all after maturity.

A molecular control system drives the cell cycle

• The cell cycle appears to be driven by specific chemical signals in the cytoplasm.

• Fusion of an S phase cell and a G1 phase cell induces the G1 nucleus to start S phase.

• Fusion of a cell in mitosis with one in interphase induces the second cell to enter mitosis

• The distinct events of the cell cycle are directed by a distinct cell cycle control system.

• These molecules trigger and coordinate key events in the cell cycle.

• The control cycle has a built-in clock, but it is also regulated by external adjustments and internal controls.

Checkpoints of cell cycle• A checkpoint in the cell cycle is a critical control point where stop and

go signals regulate the cycle.• Three major checkpoints are found in the G1, G2, and M phases.

G1 Checkpoint• For many cells, the G1 checkpoint, the restriction point in mammalian

cells, is the most important.• If the cell receives a go-ahead signal, it usually completes the cell cycle

and divides.• If it does not receive a go-ahead signal, the cell exits the cycle and

switches to a nondividing state, the G0 phase.• Most human cells are in this phase.• Liver cells can be “called back” to the cell cycle by external cues

(growth factors), but highly specialized nerve and muscle cells never divide.

• Rhythmic fluctuations in the abundance and activity of control molecules pace the cell cycle.

• Some molecules are protein kinases that activate or deactivate other proteins by phosphorylating them.

• The levels of these kinases are present in constant amounts, but these kinases require a second protein, a cyclin, to become activated.

• Levels of cyclin proteins fluctuate cyclically.• The complex of kinases and cyclin forms cyclindependent kinases

(Cdks).

G2 Checkpoint

• The G2 checkpoint prevents cells from entering mitosis when DNA is damaged

• Providing an opportunity for repair and stopping the proliferation of damaged cells.

• G2 checkpoint helps to maintain genomic stability, it is an important focus in understanding the molecular causes of cancer.

Spindle assembly checkpoints• During mitosis and meiosis, the spindle assembly checkpoint acts to

maintain genome stability by delaying cell division until accurate chromosome segregation can be guaranteed.

• Accuracy requires that chromosomes become correctly attached to the microtubule spindle apparatus via their kinetochores.

• When not correctly attached to the spindle, kinetochores activate the spindle assembly checkpoint network, which in turn blocks cell cycle progression.

• Once all kinetochores become stably attached to the spindle, the checkpoint is inactivated, which alleviates the cell cycle block and thus allows chromosome segregation and cell division to proceed.

Apoptosis• Apoptosis, or programmed cell death, is a

normal occurrence in which an orchestrated sequence of events leads to the death of a cell.

• Death by apoptosis is a neat, orderly process characterized by the overall shrinkage in volume of the cell and its nucleus, the loss of adhesion to neighboring cells, the formation of blebs at the cell surface, the dissection of the chromatin into small fragments, and the rapid engulfment of the “corpse” by phagocytosis.

• Because it is a safe and orderly process, apoptosis might be compared to the controlled implosion of a building using carefully placed explosives as compared to simply blowing up the structure without concern for what happens to the flying debris.

• It has been estimated that 1010–1011 cells in the human body die every day by apoptosis.

• For example, apoptosis is involved in the elimination of cells that have sustained irreparable genomic damage.

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References • Images references:

1. http://www.explorandomexico.com/about-mexico/8/279/

2. http://quizlet.com/18992366/mic-lecture-3-t1-flash-cards/

3. http://creationoevolution.blogspot.in/2013/02/dna-2.html

4. http://www.nature.com/scitable/definition/spindle-fibers-304

5. http://quizlet.com/16890158/cell-biology-final-exam-the-cell-cycle-and-mitosis-flash-cards/

6. http://iceh.uws.edu.au/fact_sheets/FS_gastro.html

7. http://proevolutionsoccer.cf/dna-rna

8. http://ibbiology.wikifoundry.com/page/Describe+the+events+that+occur+in+the+four+phases+of+mitosis

9. http://cc.scu.edu.cn/G2S/Template/View.aspx?courseType=1&courseId=17&topMenuId=113306&menuType=1&action=view&type=&name=&linkpageID=113784

10. http://www.biologyjunction.com/mitosis_and_meiosis.htm

11. http://bizlocallistings.com/junytd/prophase-in-an-animal-and-a-plant-cell/6

12. http://bizlocallistings.com/junytd/prophase-in-an-animal-and-a-plant-cell/6

13. http://www.jpost.com/Health-and-Sci-Tech/Health/Cancer-cells-encouraged-to-commit-suicide

14. http://www.slideshare.net/mbrown0928/cell-division-meiosis-13017412

15. http://www.nkellogg.com/apbiology.htm

16. http://science.howstuffworks.com/life/cellular-microscopic/apoptosis.htm

References

• Reading references:• Cell and Molecular Biology, 6th Ed By Karp• Molecular Cell Biology by Lodish 5th Edition