The Cell CycleChapter 12p. 228 – p.245

Important Figures12.4 p. 23012.5 p. 23112.6 p. 232 and 23312.8 p. 23512.11 and 12.12 p. 23712.13 p. 23812.14 p. 23912.17 p. 240

Important VocabGenomeBinary fissionSomatic cellsGametesChromatidChromatinCentromereMitosisCytokinesisGrowth FactorTumor (malignant v. benign)

You should be able to…Relate the roles of protein kinase,

cyclin, Cdks, and MPF in cell growth

List the steps of the cell cycle and mitosis

Describe density-dependent inhibition

Compare and contrast somatic cells with gametes.

OverviewThe continuity of life is based on the

reproduction of cells – cell division.Cell division enables sexually reproducing

organisms to develop from a single cell. Cell division continues to function after an

organism is fully grown by renewing and repairing or replacing damaged or dead cells.

Cell division is an essential part of the cell cycle.

Cell cycle – the life of a cell from the time it is first formed from a dividing parent cell until its own division into two cells.

12.1 CELL DIVISION RESULTS IN GENETICALLY IDENTICAL DAUGHTER CELLS

12.1 Cell division results in genetically identical daughter cells A cell is not like a soap bubble that simply enlarges

and splits in two. Cell division involves the distribution of identical

genetic material to two daughter cells. Genome – a cell’s endowment of DNA, it’s genetic

information. Prokaryote genome is a single long DNA molecule Eukaryotic Genome consists of a number of DNA

molecules. Before a cell can divide into genetically identical

daughter cells, all the DNA must be copied and then separated.

The replication and distribution of so much DNA is manageable because the DNA molecules are packaged into chromosomes.

12.1 Cell division results in genetically identical daughter cellsEvery eukaryotic species has a “characteristic”

number of chromosomes in each cell nucleus.Human somatic cells- all body cells except

reproductive cells- have 46 chromosomesHuman gamete cells – sperm and eggs –

have one set of 23 chromosomes.Eukaryotic chromosomes are made of

chromatin, a complex of DNA and associated protein molecules.

The associated proteins maintain the structure of the chromosome and help control the activity of the genes.

12.1 Cell division results in genetically identical daughter cells

Each duplicated chromosome has two sister chromatids.

In condensed form, the chromosome has a narrow “waist” at the centromere – a specialized region where the two chromatids are most closely attached.

Once the sisters separate, they are considered two separate chromosomes.

12.1 Cell division results in genetically identical daughter cells

Mitosis – the division of the nucleus.

Cytokinesis – the division of the cytoplasm.

Mitosis yields two identical daughter cells.

Meiosis yields non-identical daughter cells that have only one set of chromosomes.

12.2 THE MITOTIC PHASE ALTERNATES WITH INTERPHASE IN THE CELL CYCLE

12.2 The mitotic phase alternates with interphase in the cell cycleWalther Flemming, 1882, German – developed

dyes that allowed him to observe the behavior of chromosomes during mitosis and cytokinesis.

Phases of the Cell Cycle◦ Interphase

G1 phase (first gap) S phase G2 phase (second gap)

◦ Mitotic (M) phase Prophase Prometaphase Metaphase Anaphase Telophase

12.2 The mitotic phase alternates with interphase in the cell cycleInterphase often accounts for about 90% of

the cell cycle.The cell grows and copies its chromosomes

in preparation for cell division.Divided into sub phases, G1 phase (first gap),

S phase, and G2 phase (second gap).Chromosomes are only duplicated during the

S phase.Cell grows (G1), continues to grow as it

copies its chromosomes (S), grows more as it completes preparations for cell division (G2), and divides (M).

12.2 The mitotic phase alternates with interphase in the cell cycleMitosis is broken down into five

stages:◦Prophase◦Prometaphase◦Metaphase◦Anaphase◦Telophase

Cytokinesis completes the mitotic phase

12.2 The mitotic phase alternates with interphase in the cell cycle

Prophase◦ Chromatin Fibers

become more tightly coiled.

◦ Nucleoli disappear◦ Each duplicated

chromosome appears as two identical sister chromatids.

◦ The mitotic spindle begins to form.

◦ Centrosomes move away from each other.

12.2 The mitotic phase alternates with interphase in the cell cycle

Prometaphase◦ Nuclear envelope

fragments◦ Each of the two

chromatids of each chromosome now has a kinetochore

◦ Some of the microtubules attach to the kinetochores

◦ Nonkinetochore microtubules interact with those from the opposite pole of the spindle.

12.2 The mitotic phase alternates with interphase in the cell cycleMetaphase

◦ Longest stage of mitosis

◦ The centrosomes are at opposite poles of the cell

◦ The chromosomes convene on the metaphase plate. The chromosomes’ centromeres lie on the metaphase plate

12.2 The mitotic phase alternates with interphase in the cell cycle

Anaphase◦ Shortest phase◦ Begins when the cohesion

proteins are cleaved.◦ The two sister chromatids

separate and become individual chromosomes.

◦ Move to different ends of the cell as the kinetochore microtubules shorten

◦ Cell elongates as the nonkinetochore microtubules lengthen

12.2 The mitotic phase alternates with interphase in the cell cycleTelophase

◦ Two daughter nuclei form

◦ Nucleoli reappear◦ Chromosomes become

less condensed◦ Mitosis is now complete

Cytokinesis◦ Usually well underway

by late telophase◦ In animal cells,

cytokinesis involves the formation of a cleavage furrow.

12.2 The mitotic phase alternates with interphase in the cell cycle

12.2 The mitotic phase alternates with interphase in the cell cycle Many of the events of mitosis depend on the mitotic

spindle, which begins to form in the cytoplasm during prophase.

Fibers made of microtubules and associated proteins. In animal cells, the assembly of spindle microtubules

start at the centrosome. A pair of centrioles is located at the center of the

centrosome but are not essential for cell division. Aster – radial array of short microtubules - extends

from each centrosome. Kinetochore – structure of proteins associated with

specific sections of chromosomal DNA at the centromere.

Metaphase plate – Imaginary plane of the cell midway between the spindle’s two poles.

12.2 The mitotic phase alternates with interphase in the cell cycle

12.2 The mitotic phase alternates with interphase in the cell cycleIn animal cells, cytokinesis occurs by a

process known as cleavageFirst sign – cleavage furrow.On the cytoplasmic side of the furrow is a

contractile ring of actin microfilaments associated with molecules of the protein myosin

The actin microfilaments interact with the myosin molecules, causing the ring to contract.

Plants form a cell plate instead of a cleavage furrow.

12.2 The mitotic phase alternates with interphase in the cell cycle

Binary Fission Binary fission – division

in half Single-celled eukaryotes

and Prokaryotes reproduce by binary fission. Prokaryotes do not include mitosis.

Bacterial chromosome consist of a circular DNA molecule and proteins.

Origin of replication - a particular sequence in a genome at which replication is initiated.

12.2 The mitotic phase alternates with interphase in the cell cycle

Evolution of MitosisProkaryotes preceded

Eukaryotes, so mitosis had its origins in simpler prokaryotic mechanisms of cell reproduction.

Some of the proteins involved in bacterial binary fission are related to eukaryotic proteins that function in mitosis support this hypothesis.

12.3 THE EUKARYOTIC CELL CYCLE IS REGULATED BY A MOLECULAR CONTROL SYSTEM

12.3 The eukaryotic cell cycle is regulated by a molecular control systemThe timing and rate of cell division in different parts

of a plant or animal are crucial to normal growth, development, and maintenance.

Frequency of cell division varies with the type of cell. Cell cycle differences result from regulation at the

molecular level. Paul Nurse thought one hypothesis might be that

each event in the cell cycle merely leads to the next – a simple metabolic pathway.

In the early 1970, a variety of experiments led to an alternative hypothesis: the cell cycle is driven by specific signaling molecules present in the cytoplasm.

Mammalian cells grown in culture

12.3 The eukaryotic cell cycle is regulated by a molecular control systemCell Cycle Control system – a cyclically

operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle.

Cell cycle is regulated at certain checkpoints by both internal and external signals.

Checkpoint- a control point where stop and go-ahead signals can regulate the cycle.

Three major checkpoints are found in the G1, G2, and M phases.

12.3 The eukaryotic cell cycle is regulated by a molecular control systemThe G1 Checkpoint

seems to be the most important.

Nondividing stage is called the G0 phase.◦Most cells of the human

body are in this phase.If a cell passes the G1

checkpoint, it will usually complete the G1, S, G2, and M phases and divide.

12.3 The eukaryotic cell cycle is regulated by a molecular control systemCyclins and Cyclin-Dependent Kinases

Rhythmic fluctuations in the abundance and activity of cell cycle control mmolecules pace the sequential events of the cell cycle.

Mainly proteins of two types: protein kinases and cyclins.

Protein kinases – enzymes that activate or inactivate other proteins by phosphorylating them.

Many kinases that drive the cell cycle are actually present at a constant concentration in the growing cell, but are in an inactive form most of the time.

12.3 The eukaryotic cell cycle is regulated by a molecular control systemTo be active, a kinase must be attached to a

cyclin.Cyclin – a protein that gets its name from its

cyclically fluctuating concentration in the cell. Cdks – cyclin-dependent kinases.The activity of a Cdk rises and falls with

changes in the concentration of its cyclin partner.

MPF – the cyclin-Cdk complex that was discovered first.

Peaks of MPF activity correspond to the peaks of cyclin concentration.

12.3 The eukaryotic cell cycle is regulated by a molecular control system

Figure 12.7 (a) p. 240

12.3 The eukaryotic cell cycle is regulated by a molecular control systemThe initials MPF stand for “maturation-

promoting factor”. Think of it as “M-phase promoting factor” since it triggers the cell’s passage past the G2 checkpoint into M phase.

When cyclins that accumulate during G2 associate with Cdk molecules: MPF complex phosphorylates a variety of proteins, initiating mitosis.

Directly as a kinase, indirectly by activating other kinases.

12.3 The eukaryotic cell cycle is regulated by a molecular control systemMPF causes phosphorylation of various

proteins of the nuclear lamina.Chromosome condensation and spindle

formation.Anaphase – MPF helps switch itself off

by initiating a process that leads to the destruction of its own cyclin.

Cell behavior control at G1 checkpoint?◦Animal cells have at lease three Cdk

proteins and several different cyclins that operate at this checkpoint.

12.3 The eukaryotic cell cycle is regulated by a molecular control systemStop and Go signalsGrowth factor – a protein released by

certain cells that stimulates other cells to divide. (more than 50).

Density-dependent inhibition – a phenomenon in which crowded cells stop dividing

Anchorage dependence – The requirement that a cell must be attached to a substratum in order to divide.

12.3 The eukaryotic cell cycle is regulated by a molecular control systemCancer cellsCancer cells elude normal regulation

and divide out of control.Malignant tumors invade surrounding

tissues and can metastasize, exporting cancer cells to other parts of the body.

Malignant – cancerousBenign – not cancerousMetastasis – the spread of cancer cells

to locations distant from their original site.

MEIOSIS AND SEXUAL LIFE CYCLEChapter 13 p. 248 to p. 260

IMPORTANT FIGURES

13.3 13.4 13.6 13.7 13.8 13.9 13.12

IMPORTANT VOCAB Gene Karyotype Homologue Sex

Chromosome Autosome Gamete Fertilization Haploid

• Diploid• Polyploid• Zygote• Synapsis• Tetrad• Crossing

Over• Chiasma

OVERVIEW: VARIATIONS ON A THEME

Heredity – The transmission of traits from one generation to the next.

Variation – Difference between members of the same species.

Genetics – the scientific study of heredity and hereditary variation.

13.1 OFFSPRING ACQUIRE GENES FROM PARENTS BY INHERITING CHROMOSOMES

13.1 OFFSPRING ACQUIRE GENES FROM PARENTS BY INHERITING CHROMOSOMES

Parents do not say “Here, let’s give him/her my freckles”.

Parents endow their offspring with coded information in the form of hereditary units called genes.

Genes program the specific traits that emerge as organisms develop from the smallest stage of life to the end.

13.1 OFFSPRING ACQUIRE GENES FROM PARENTS BY INHERITING CHROMOSOMES

Inheritance of Genes Genetic program is written in DNA. Specific sequence of DNA nucleotides Gametes – reproductive cells of plants

and animals. DNA of a eukaryotic cell is packaged into

chromosomes within the nucleus. Locus – a gene’s specific location along

the length of a chromosome.

13.1 OFFSPRING ACQUIRE GENES FROM PARENTS BY INHERITING CHROMOSOMES

Asexual reproduction – exact copies Asexual reproduction - a single individual is

the sole parent and passes copies of all its genes to its offspring.

An individual that reproduces asexually gives rise to a clone: a group of genetically identical individuals

Sexual reproduction – two parents give rise to offspring that have unique combinations of genes inherited from the two parents.

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Life cycle – generation to generation sequence of stages in the reproductive history of an organism.

Somatic cell- any cell other than those involved in gamete formation. Humans have 46

There are two chromosomes of each 23 types.

Karyotype – A display of the chromosome pairs of a cell arranged by size and shape.

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Homologous chromosomes – A pair of chromosomes of the same length, centromere position, and staining pattern that possess genes for the same characters at corresponding loci.

Sex Chromosomes – XY, XX Autosomes – all other chromosomes.

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Inherit one chromosome of each pair from each parent.

The number of chromosomes represented by a single set – n

Diploid cell – any cell with two chromosome sets and has a diploid number of chromosomes, 2n.

Haploid cell – single chromosome set, e.g. gametes (sperm and eggs)

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Figure 13.4

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Fertilization – The union of haploid gametes to produce a diploid zygote

Zygote – resulting egg, diploid. The only cells of the human body not produced

by mitosis are gametes. Gametes develop from specialized cells called

germ cells in the gonads. Meiosis – cell division in sexually reproducing

organisms that consists of two rounds of cell division and one round of DNA replication.

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

The Variety of Sexual Life Cycles Timing of alternation of meiosis and fertilization

varies Three main types Alternation of generations – A life cycle in

which there is both a multicellular diploid form, the sporophyte, and a multicellular haploid form, the gametophyte.

Sporophyte – diploid stage Spore – haploid cells Gametophyte – multicellular haploid stage

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

The sporophyte generation produces a gametophyte as its offspring, and the gametophyte produces the next sporophyte generation.

Third : After gametes fuse and form a diploid zygote, meiosis

occurs without a multicellular diploid offspring developing.

Meiosis produces haploid cells that then divided by mitosis.

This gives rise to either unicellular descendants or a haploid multicellular adult organism.

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Figure 13.6

Diploidmulticellular

organism

Key

MEIOSIS FERTILIZATION

MEIOSIS FERTILIZATION

MEIOSIS FERTILIZATION

n

n

n

n n

n

n n

nn

n

n

n

2n2n

2n 2n2nZygote

GametesHaploid multicellular

organism (gametophyte)Haploid multicellular

organism

HaploidDiploid

Mitosis Mitosis

SporesGametes

Mitosis Mitosis

Gametes

Mitosis

Zygote

ZygoteMitosis

(a) Animals

Diploidmulticellularorganism(sporophyte)

(b) Plants and some algae (c) Most fungi and some protists

13.2 FERTILIZATION AND MEIOSIS ALTERNATE IN SEXUAL LIFE CYCLES

Either haploid or diploid cells can divide by mitosis depending on the life cycle.

Only diploid cells can undergo meiosis.

Share fundamental result: genetic variation among off-spring.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Meiosis I and Meiosis II Result in four daughter cells Alleles – different versions of genes that

appear alike. Homologs are not associated with each

other except during meiosis. Sister chromatids are two copies of one

chromosome. Together they make up one replicated chromosome.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Figure 13.7

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Prophase I In synapsis, homologous chromosomes

loosely pair up, aligned gene by gene. In crossing over, nonsister chromatids

exchange DNA segments Each pair of chromosomes forms a tetrad,

a group of four chromatids: AABB CCDD Each tetrad usually has one or more

chiasmata, X-shaped regions where crossing over occurred.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Metaphase I In metaphase I, tetrads line up randomly at

the metaphase plate, or middle. Microtubules from one pole are attached to

the kinetochore of one chromosome of each tetrad.

Microtubules from the other pole are attached to the kinetochore of the other chromosome.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Anaphase I Pairs of homologous chromosomes

separate One chromosome moves toward each pole,

guided by the spindle apparatus: depolymerization of the spindle fibers’ microtubules

Sister chromatids remain attached at the centromere and move as one unit toward the pole.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Telophase I and Cytokinesis In the beginning of telophase I, each half of

the cell has a haploid set of chromosomes; each chromosome still consists of two sister chromatids

Cytokinesis usually occurs simultaneously, forming two haploid daughter cells.

Animal: cleavage furrow. Plant: cell plate No chromosomes replicate between the

end of meiosis I and the beginning of meiosis II.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Meiosis II occurs in 4 stages Prophase II Metaphase II Anaphase II Telophase II and cytokinesis

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Prophase II Spindle apparatus

forms Chromosomes move

towards the metaphase plate

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Metaphase II Sister chromatids

lined up at metaphase plate

Sister chromatids are no longer genetically identical due to crossing over

Microtubules attach to kinetochores

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Anaphase II Sister chromatids

separate The new individual

chromosomes move to opposite poles

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Telophase II Chromosomes arrive

at opposite poles and decondense

Nuclei form

Cytokinesis Cytoplasm separated

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Synapsis and Crossing Over: Prophase I, replicated homologs pair up

and become physically connected. Zipper like protein structure –

synaptonemal complex . Process called synapsis.

Crossing over The two homologs pull apart slightly but

remain connected at a X-shaped region called the chiasma.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Homologs on the metaphase plate: At metaphase I, chromosomes are

positioned on the metaphase plate. Pairs of homologs rather than individual

chromosomes.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Separation of homologs: Anaphase I Replicated chromosomes of each

homologous pair move toward opposite poles

Sister chromatids of each replicated chromosome remain attached.

13.3 MEIOSIS REDUCES THE NUMBER OF CHROMOSOME SETS FROM DIPLOID TO HAPLOID

Sister chromatids are attached along their lengths by protein complexes called cohesions

Released in two steps Anaphase I: cohesions are cleaved along

the arms. Homologs separate Anaphase II: cohesions are cleaved at the

centromeres. Chromatids separate.

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

Mutations are the original source of genetic diversity

Create different versions of genes called alleles

Recombinations – reshuffling of alleles during sexual reproduction produces genetic variation

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

Three mechanisms in Sexual Reproduction contribute to genetic variation: Independent assortment Crossing over Random fertilization

For humans (n= 23), there are more than 8 million (223) possible combinations of chromosomes

INDEPENDENT ASSORTMENT

Figure 13.11

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

Crossing over produces recombinant chromosomes, which combine genes inherited from each parent.

Crossing over begins very early in prophase I, as homologous chromosomes pair up gene by gene.

In crossing over, homologous portions of two nonsister chromatids trade places

Crossing over contributes to genetic variation by combining DNA from two parents into a single chromosome.

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

Figure 13.12

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

Random fertilization adds to genetic variation because any sperm can fuse with any ovum.

The fusion of two games produces a zygote with any of about 70 trillion diploid combinations

13.4 GENETIC VARIATION PRODUCED IN SEXUAL LIFE CYCLES CONTRIBUTES TO EVOLUTION

Natural selection results in the accumulation of genetic variations favored by the environment.

Sexual reproduction contributes to the genetic variation in a population, which originates from mutations.

COMPARING MITOSIS AND MEIOSIS

Figure 13.9

COMPARING MITOSIS AND MEIOSISFigure 13.9