Cell biology and genetics Unit 2Cell cycle and Cancer

Rai University, Ahmedabad

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Cell DivisionAll cells are derived from pre-

existing cells

New cells are produced for growthand to replace damaged or old cells

Differs in prokaryotes (bacteria) andeukaryotes (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 acomplete set of the DNA molecules

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DNA Replication

DNA must be copied orreplicated before cell division

Each new cell will then have an identical copyof 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 chromosomeattached 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 aroundproteins 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 Cycle

G1 - primary growth phase

S – synthesis; DNA replicated

G2 - secondary growth phase

collectively these 3 stages are called interphase

M - mitosis

C - cytokinesis

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Interphase - G1 Stage

1st growth stage after cell division

Cells mature by making more cytoplasm & organelles

Cell carries on its normal metabolic activities

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Interphase – S Stage

Synthesis stage

DNA is copied or replicated

Two identical copies of DNA

Original DNA

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Interphase – G2 Stage2nd Growth Stage

Occurs after DNA has been copied

All 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 Prophase Chromatin in nucleus condenses to form visible

chromosomes

Mitotic spindle forms from fibers in cytoskeleton or centrioles (animal)

Chromosomes

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Late Prophase

Nuclear membrane & nucleolus are broken down

Chromosomes continue condensing & are clearly visible

Spindle fibers called kinetochores attach to the centromere of each chromosome

Spindle 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 cell

Chromosomes 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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Anaphase

Occurs rapidly

Sister 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

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Telophase

Sister chromatids at opposite poles

Spindle disassembles

Nuclear envelope forms around each set of sister chromatids

Nucleolus reappears

CYTOKINESIS occurs

Chromosomes reappear as chromatin

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Comparison of Anaphase & Telophase

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CytokinesisMeans division of the cytoplasm

Division of cell into two, identical halves called daughter cells

In plant cells, cell plate forms at the equator to divide cell

In animal cells, cleavage furrow forms to split cell

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Daughter Cells of Mitosis

Have 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 replication

Two meiotic divisions --- Meiosis I and Meiosis II

Called Reduction- division

Original cell is diploid (2n)

Four daughter cells produced that are monoploid (1n)

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Facts About Meiosis

Daughter cells contain half the number of chromosomes as the original cell

Produces 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 reproduction

Two 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

half

Fertilization 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

MeiosisI

MeiosisII

Diploid

Haploid

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Meiosis I: Reduction Division

Nucleus Spindlefibers

Nuclearenvelope

Early Prophase I(Chromosome number doubled)

Late Prophase I

Metaphase I

Anaphase 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 I

Homologous 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 pairsof 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 II

Telophase 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 chromatidsseparate and move to opposite poles.

Equator

Pole

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Telophase II

Nuclear 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 12

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