The Cell Cycle

Core Concepts• Cell division is necessary for reproduction, repair and growth.Cell division is necessary for reproduction, repair and growth.• The cell cycle is a continuum of processes undergone by cells during The cell cycle is a continuum of processes undergone by cells during

their lifetime, which involves growth and functioning, and culminates in their lifetime, which involves growth and functioning, and culminates in division.division.

• Mitosis produces two new identical cells.Mitosis produces two new identical cells.• Interactions of physical and chemical signals control the events of the Interactions of physical and chemical signals control the events of the

cell cycle.cell cycle.• Cancer results from abnormal or lacking control signals 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-Meiosis is a special kind of division that produces four (4) haploid, non-

identical cells.identical cells.• Errors may occur during cell division, producing cells with abnormal Errors may occur during cell division, producing cells with abnormal

chromosome number.chromosome number.

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

The Cell CycleRoles of Cell Division

• Growth and development

• Reproduction • Renewal and repair

The Cell CycleTypes of cell division• Mitosis

– May have evolved from binary fission in prokaryotes

– Method of asexual reproduction in unicellular eukaryotes

• Meiosis– Responsible for

production of gametes in multicellular eukaryotes

The Cell CycleStages of the cell cycle

Important terms• genome - genetic material of a cell• chromatin – unorganized mass of DNA

and proteins that condense 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)• interphase – preparation for cell

division – cell grows– DNA is replicated– centrosomes are replicated*– chromosomes condense

Eukaryotic cell division• 1 chromosome 2

sister chromatids, connected at a centromere, which separate during cell division

• mitosis – division of the nucleus

• cytokinesis – division of cytoplasm

Mitosis consists of five distinct phases– Prophase– Prometaphase

G2 OF INTERPHASE PROPHASE PROMETAPHASE

Centrosomes(with centriole pairs) Chromatin

(duplicated)

Early mitoticspindle

Aster

CentromereFragmentsof nuclearenvelope

Kinetochore

Nucleolus Nuclearenvelope

Plasmamembrane

Chromosome, consistingof two sister chromatids

Kinetochore microtubule

Nonkinetochoremicrotubules

– Metaphase– Anaphase– Telophase

Centrosome at one spindle pole

Daughter chromosomes

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Spindle

Metaphaseplate

Nucleolusforming

Cleavagefurrow

Nuclear envelopeforming

Mitosis in a plant cell

1Prophase. The chromatinis condensing. The nucleolus is beginning to disappear.Although not yet visible in the micrograph, the mitotic spindle is staring to from.

Prometaphase.We now see discretechromosomes; each consists of two identical sister chromatids. Laterin prometaphase, the nuclear envelop will fragment.

Metaphase. The spindle is complete,and the chromosomes,attached to microtubulesat their kinetochores, are all at the metaphase plate.

Anaphase. Thechromatids of each chromosome have separated, and the daughter chromosomesare moving to the ends of cell as their kinetochoremicrotubles shorten.

Telophase. Daughternuclei are forming. Meanwhile, cytokinesishas started: The cellplate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell.

2 3 4 5

NucleusNucleolus

ChromosomeChromatincondensing

Regulation of the Cell Cycle• Events in the cell cycle

triggered and coordinated by a molecular control system

• Checkpoints – critical control points where stop and go-ahead signals can regulate the cycle

Restriction Point

Factors that control the cell cycle1. 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 cycle2. Regulatory proteins• Cyclins - concentration

cyclically 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 cycle3. Growth Factors• proteins that stimulate other cells to divide • promote the binding of cyclin to cdks• ex. platelet-derived growth factor (PDGF)

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 Cancer – uncontrolled cell divisiondivision• Cells do not heed Cells do not heed

normal signals to STOP normal signals to STOP cell divisioncell division

• Can invade neighboring Can invade neighboring cells and interfere with cells and interfere with normal body functionnormal body function

• ““immortal” – can keep immortal” – can keep dividing as long as dividing as long as nutrient supply is kept nutrient supply is kept constantconstant

Transformation

• Numerous diverse Numerous diverse causescauses

• Cancer cell Cancer cell tumor tumor– BenignBenign– MalignantMalignant

• MetastasisMetastasis

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

MeiosisReductional Division for Sexual Reproduction

• Types of reproduction– Asexual– Sexual

• Genes – hereditary units of DNA

• Locus – gene’s specific location in the chromosome

Meiosis in Sexual Life Cycles• Generation-to-generation

sequence of stages in the reproductive history of an organism

• Homologous chromosomes – pair that has the same length, centromere position, staining pattern

• 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 is reductional cell division

Crossing-over during Prophase IExchange 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

Meiosis II is equational cell division

How unique are you?

• Random fertilization– 1/64 million

• Independent assortment– 1/223

• Crossing-over– occurs an average of 2-3 times

per chromosome pair

Gametogenesis1) Meiosis

- Gametes (n) formed from embryonic primordial germ cells (PGC’s) via meiosis

- PGC’s (2n) meiosis sex cells (n)

- Spermatogonium and oogonium

2) Maturation– distinctive characteristics of

sperm and egg cells are formed

Spermatogenesis vs. OogenesisSPERMATOGENESIS

process is continuous100-650 million sperm cells

produced

OOGENESISunequal cytokinesistime tableonly 400 oocytes ovulated

between puberty & menopause

Spermatogenesis vs. Oogenesis

Suspended in prophase I

One oocyte / month

Halted at metaphase II until fertilization

2N

N

N

OOGENESIS

2 million 1o oocytes in a fetus

1 million 1o oocytes in a newborn (at prophase I)

400,000 1o oocytes during puberty(meiosis I completed in only one each month)

400 2o oocytes ovulated (at metaphase II)between puberty and menopause

(meiosis II completed only after fertilization)

mature ovum

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:• Pairs of

homologous chromosomes do not separate normally during meiosis

• Gametes contain two copies or no copies of a particular chromosome

Meiosis I

Nondisjunction

Meiosis II

Nondisjunction

Gametes

n + 1n + 1 n 1 n – 1 n + 1 n –1 n n

Number of chromosomes

Nondisjunction of homologouschromosomes in meiosis I

Nondisjunction of sisterchromatids in meiosis II

(a) (b)

• Aneuploidy– Results from the fertilization of

gametes in which nondisjunction occurred

– Is a condition in which offspring have an abnormal number of a particular chromosome

• If a zygote is trisomic– It has three copies of a particular

chromosome• If a zygote is monosomic

– It has only one copy of a particular chromosome

• Klinefelter (XXY), Turner (X0)

• The incidence of Down syndrome in the general population is about 1 in every 770 births.

• Among women over the age of 35 years, however, the incidence of delivering a child with Down syndrome increases.

• The correlation between maternal age and Down syndrome risk is striking when the age distribution for all mothers for all mothers is compares to that of mothers of Down syndrome children.

• 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