The Cell Cycle

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Core Concepts • Cell division is necessary for reproduction, repair and growth.

• The cell cycle is a continuum of processes undergone by cells

during their lifetime, which involves growth and functioning,

and culminates in division.

• Mitosis produces two new identical cells.

• Interactions of physical and chemical signals control the events

of the cell cycle.

• Cancer results from abnormal or lacking control signals of the

cell cycle.

• Meiosis is a special kind of division that produces four (4)

haploid, non-identical cells.

• Errors may occur during cell division, producing cells with

abnormal chromosome number. www.brookes.ac.uk

Keywords

• anaphase

• centromere

• chromatin

• chromosome

• crossing-over

• cytokinesis

• diploid

• G1

• G2

• genome • haploid • homologue • interphase • kinetochore • meiosis • metaphase • mitosis

• non-disjunction • prophase • sister chromatid

• spindle • synthesis • telophase • tetrad

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Cell

Reproduction

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“Where a cell exists, there must

have been a preexisting cell…”

-Rudolf Virchow

Roles of Cell Division

Reproduction

Growth and development

Renewal and repair

poosk.com,

www.telegraph.co.uk,

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Types of cell division

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The Cell Cycle -ordered series of events that leads to

cell growth, division, and replication

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interphase

–preparation for cell division

–cell grows

–DNA is replicated

–centrosomes are replicated*

7

• chromatin –

unorganized mass of

DNA and proteins

that condenses

during cell division

• chromosomes – packaged DNA

molecules in nuclei

– somatic cells

have 2 sets of

chromosomes (2N,

diploid)

– gametes have 1

set of

chromosomes (N,

haploid)

Chromosomes vs. Chromatin

What

happens to

the DNA

during cell

division?

Unduplicated

chromosome

(End of G1)

Duplicated

chromosome

(End of S)

Daughter

cells with

identical

chromosomes

(End of M)

its sister chromatid

one sister chromatid

centromere (point of attachment)

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Eukaryotic Cell Division

Mitosis (division of the nucleus)

Prophase

Metaphase

Anaphase

Telophase Cytokinesis

(division of the cytoplasm)

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Overview of cell division in animal cells

Overview of cell division in a plant cell

Nucleus

Nucleolus Chromosome Chromatin

condensing

Cell plate

formation

• No centrioles/centrosomes

• Formation of a cell plate

Interphase Prophase Metaphase Anaphase Telophase and

Cytokinesis

Regulation of the Cell Cycle

• Molecular control

system

• Checkpoints – critical

control points where

stop and go-ahead

signals can regulate

the cycle

Restriction Point

point of no return

1. Sufficient growth?

2. Suitable environment?

3. Undamaged DNA?

Before

chromosomes

condense

1. DNA

replicated?

2. Sufficient

growth?

Factors that control the cell cycle

1. Telomeres

– Repeated DNA

sequences at tips of

chromosomes

– TTAGGG sequences lost

every time a cell divides

– Restored to their

original length by

telomerase (normally

found in gametes)

Factors that control the cell cycle

2. Regulatory proteins

• Cyclins - concentration

fluctuates in the cell

• Cyclin-dependent

kinases (Cdks) –

activate other proteins in the

presence of cyclin

• e.g. Maturation-promoting

factor (MPF)

– M-phase promoted

• Chromatin condensation

• Mitotic spindle formation

• Degradation of nuclear

envelope

– Deactivated when proteolytic

enzymes digest the cyclin

Factors that control the cell cycle 3. Growth Factors

• proteins that stimulate other cells to divide

• promote the binding of cyclin to cdks

• ex. platelet-derived growth factor (PDGF),

epidermal growth factor (EGF)

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Factors that control the cell cycle

4. Density-dependent

inhibition

5. Anchorage dependence • Most animal cells must be

attached to a substrate before

they can grow

Cancer Uncontrolled cell division

• Cells do not heed

normal signals to STOP

cell division

• Can invade neighboring

cells and interfere with

normal body function

• “immortal” – can keep

dividing as long as

nutrient supply is kept

constant

http://upload.wikimedia.org/wikipedia/en/1/1f/Normal_cancer_cell_differences_from_NIH.png

Transformation

• Numerous diverse

causes

• Cancer cell

tumor

– Benign

– Malignant

• Metastasis

Causes

• Oncogenes – Gene that enables

transformation when mutated

or expressed in high levels

• Viruses and bacteria – e.g. HPV and cervical cancer;

Hep B and C and liver cancer;

H.pylori and stomach cancer

• Ionizing and UV

radiation

• Carcinogens

Treatment

• Surgery

• Radiation

• Chemotherapy

• Immunotherapy

and gene therapy

Meiosis Reductional Division for Sexual

Reproduction

• Types of reproduction

– Asexual

– Sexual

• gene – hereditary unit

of DNA

Meiosis in

Sexual Life Cycles

• Homologous

chromosomes

– pair that has the same

length, centromere position,

staining pattern

– contain similar sets of

information

• Humans

– 22 pairs of autosomes

– 1 pair of sex

chromosomes

Meiosis involves 2

stages of nuclear

division

• Interphase

–G1, S, G2

• Meiosis

–Meiosis I

–Meiosis II

Meiosis I Separating

homologous

chromosomes

Meiosis I Separating

homologous

chromosomes

Meiosis I Separating

homologous

chromosomes

Meiosis I Separating

homologous

chromosomes

Meiosis I is reductional cell division

Crossing-over during Prophase I Exchange of segments between homologous pairs

• Homologues pair up

tetrad

• Synapsis

“crossing-over” that

occurs at a chiasma

• Does not normally

happen to sex

chromosomes

• Purpose: to increase

genetic variation

Independent assortment during Metaphase I Random separation of homologous chromosomes

Meiosis II is equational cell division

Property Mitosis Meiosis

DNA replication Interphase before mitosis Interphase before Meiosis I

Number of divisions One, including PMAT Two, each including PMAT

Synapsis of homologous chromosomes

Does not occur Prophase I; along with crossing-over

Number of daughter cells and genetic composition

Two, each diploid (2n), genetically identical to parent cell

Four, each haploid (n), half as many chromosomes as parent cell, genetically unique

Role in the animal body

Adult from zygote, produces cells for growth, repair; asexual reproduction

Produces gametes and introduces genetic variability among gametes

How unique are you?

• Random fertilization

– 1/2,000,000 egg cells x

1/4,000,000,000 sperm cells

• Independent assortment

– 1/223 unique chromosome

combination

• Crossing-over

– occurs an average of 2-3 times

per chromosome pair

Human gametogenesis Production of gametes

Mitosis (1 diploid cell 2 diploid cells)

Meiosis I (1 diploid cell 2 haploid cells)

Meiosis II (2 haploid cells 4 haploid cells)

Maturation and differentiation (haploid cells undergo extensive changes and organization)

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Primordial germ cell in embryo (2N)

Spermatogonium (2N) Oogonium (2N)

Primary spermatocyte (2N)

Primary oocyte (2N)

Secondary spermatocytes (N)

Secondary oocyte (N)

Spermatids (N) Ootid (N)

Spermatozoa (N) Ovum (N)

Spermatogenesis Oogenesis

Spermatogenesis

• Equal cytokinesis

• Continuous

• 100-650 million sperm cells

produced

Oogenesis

• Unequal cytokinesis

• Time table

• 400 oocytes ovulated

between puberty and

menopause 2 million 1 million

400,000 Suspended in prophase I before birth

One oocyte / month completes meiosis I

400 ovulated from

puberty to

menopause Halted at metaphase II until

fertilization

Only present after

fertilization

Questions:

• How many sets of chromosomes are present in each of

the following cell types?

– an oogonium

– a 1o spermatocyte

– a spermatid

– a cell during anaphase I, from either sex

– a cell during anaphase II, from either sex

– a 2o oocyte

– a polar body derived from a 1o oocyte

• Why is it extremely unlikely that a child will be

genetically identical to a parent?

Questions:

• How do the structures of the male and female gametes

aid in their functions?

• A woman who is about 4 weeks pregnant suddenly

begins to bleed and pass some tissue through her

vagina. After a physician examines the material, he

explains to her that a sperm fertilized a polar body

instead of an ovum, and an embryo could not develop.

What has happened? Why do you think a polar body

cannot support the development of an embryo, whereas

an ovum, which is genetically identical to it, can?

Errors in cell division Chromosomal aberrations

Nondisjunction

• Failure to separate

normally

– pairs of homologous

chromosomes during

meiosis I

– sister chromatids fail

to separate in meiosis

II and mitosis

• Gametes contain two

copies or no copies of

a particular

chromosome

• What happens when

these gametes are

fertilized?

Aneuploidy

– offspring have an abnormal number

of a particular chromosome

– fertilization of gametes in which

nondisjunction occurred

• Trisomic zygote

• three copies

of a

particular

chromosome

(e.g.

Trisomy-21,

Trisomy-X)

• Monosomic

zygote

• one copy of

a particular

chromosome

(e.g.

Monosomy

X)

• Incidence of Down syndrome

1 in every 770 births.

• Among women over the age

of 35 years, incidence of

delivering a child with Down

syndrome increases.

Can sometimes occur in the early stages of

embryonic development

2N 2N 2N

2N 2N+1 2N-1

Polyploidy

– Extra sets of chromosomes

(3n, 4n, 5n, 6n, 8n, 10n, 12n)

– Caused by nondisjunction of

ALL chromosomes

• Rare, usually fatal in animals

• Common in plants (30-80%)

– Polyploids often thrive

better and grow taller

– Solution to hybrid sterility

– May be preferred because of

sterility