The Cell Cycle - AP Biology · The cell cycle is driven by specific signaling molecules present in...

CAMPBELL BIOLOGY IN FOCUS

Urry • Cain • Wasserman • Minorsky • Jackson • Reece

Lecture Presentations by

Kathleen Fitzpatrick and Nicole Tunbridge

9The Cell Cycle

Overview: The Key Roles of Cell Division

The ability of organisms to produce more of their

own kind best distinguishes living things from

nonliving matter

The continuity of life is based on the reproduction

of cells, or cell division

Reproduction

In unicellular organisms, division of one cell

reproduces the entire organism

Development and Maintenance

Cell division enables multicellular eukaryotes to

develop from a single cell and, once fully grown, to

renew, repair, or replace cells as needed

Cell division is an integral part of the cell cycle, the

life of a cell from formation to its own division

Figure 9.2

(a) Reproduction

(c) Tissue renewal

(b) Growth anddevelopment

Concept 9.1: Most cell division results in genetically identical daughter cells

Most cell division results in the distribution of

identical genetic material—DNA—to two daughter

Mitosis – identical daughter cells

Meiosis – slightly different daughter cells

Cellular Organization of the Genetic Material

There are many terms for genetic material

All the DNA in a cell constitutes the cell’s genome

A genome can consist of a single DNA molecule

(common in prokaryotic cells) or a number of DNA

molecules (common in eukaryotic cells)

DNA molecules in a cell can

condense into chromosomes

Eukaryotic chromosomes

MORE Terms and Concepts Related to Genetic Material

Eukaryotic chromosomes consist of chromatin, a

complex of DNA and protein

Every eukaryotic species has a characteristic

number of chromosomes in each cell nucleus

Somatic cells (nonreproductive cells) have two sets

of chromosomes

Gametes (reproductive cells: sperm and eggs) have

one set of chromosomes

Distribution of Chromosomes During Eukaryotic Cell Division

To prepare for cell division, DNA is replicated, then

chromosomes condense

Each duplicated chromosome has two sister

chromatids (chromatids are identical).

The centromere is where the two chromatids are

most closely attached

Centromere 0.5 m

Sisterchromatids

During cell division,

the two sister

chromatids of each

duplicated

chromosome

separate and move

into two nuclei

Once separate, the

chromatids are

called

chromosomes

Figure 9.5-1

Centromere

ChromosomalDNA moleculesChromosomes

Chromosome

Figure 9.5-2

Centromere

Sisterchromatids

Chromosome

Chromosome duplication

Figure 9.5-3

Centromere

Sisterchromatids

Separation of sisterchromatids

Chromosome

Chromosome duplication

Eukaryotic cell division consists of

Mitosis, the division of the genetic material in the

nucleus

Cytokinesis, the division of the cytoplasm

Meiosis Prepares for Sexual Reproduction

Gametes are produced by a variation of cell division

called meiosis

Meiosis yields nonidentical daughter cells that have

only one set of chromosomes, half as many as the

parent cell

Concept 9.2: The mitotic phase alternates with interphase in the cell cycle

In 1882, the German anatomist Walther Flemming

developed dyes to observe chromosomes during

mitosis and cytokinesis

Phases of the Cell Cycle

The cell cycle consists

Mitotic (M) phase,

including mitosis and

cytokinesis

Interphase, including

cell growth and

copying of

chromosomes in

preparation for cell

division

S(DNA synthesis)

Interphase (about 90% of

the cell cycle) can be

divided into subphases

G1 phase (“first gap”)

S phase (“synthesis”)

G2 phase (“second gap”)

The cell grows during all

three phases, but

chromosomes are

duplicated only during the

S(DNA synthesis)

Mitosis is conventionally divided into five phases

Prophase

Prometaphase

Metaphase

Anaphase

Telophase

Cytokinesis overlaps the latter stages of mitosis

Video: Animal Mitosis

Video: Microtubules Mitosis

VIDEO: Mitosis

Video: Microtubules Anaphase

Video: Nuclear Envelope

Figure 9.7a

Centrosomes(with centriolepairs)

G2 of Interphase Prophase Prometaphase

Chromosomes(duplicated,uncondensed)

Early mitoticspindle

Centromere

Fragmentsof nuclearenvelope

Nonkinetochoremicrotubules

Kinetochoremicrotubule

KinetochoreNucleolusPlasmamembrane Two sister chromatids of

one chromosome

Nuclearenvelope

Figure 9.7b

Metaphase Anaphase Telophase and

Cytokinesis

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming

Spindle Centrosome atone spindle pole

Daughterchromosomes

Metaphaseplate

Figure 9.7c

Centrosomes(with centriolepairs)

G2 of Interphase Prophase

Chromosomes(duplicated,uncondensed)

Early mitoticspindle

Centromere

NucleolusPlasmamembrane Two sister chromatids of

one chromosome

Nuclearenvelope

Figure 9.7d

Prometaphase

Fragmentsof nuclearenvelope

Nonkinetochoremicrotubules

Kinetochore Spindle Centrosome atone spindle pole

Metaphaseplate

Metaphase

Figure 9.7e

Anaphase Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming

Daughterchromosomes

Figure 9.7f

G2 of Interphase

Figure 9.7g

Prophase

Figure 9.7h

Prometaphase

Figure 9.7i

Metaphase

Figure 9.7j

Anaphase

Figure 9.7k

Telophase and Cytokinesis

The Mitotic Spindle: A Closer Look

The mitotic spindle is a structure made of

microtubules and associated proteins

It controls chromosome movement during mitosis

In animal cells, assembly of spindle microtubules

begins in the centrosome, the microtubule

organizing center

Cytoskeleton Preparations

The centrosome replicates during interphase,

forming two centrosomes that migrate to opposite

ends of the cell during prophase and prometaphase

An aster (radial array of short microtubules) extends

from each centrosome

The spindle includes the centrosomes, the spindle

microtubules, and the asters

During prometaphase, some spindle microtubules

attach to the kinetochores of chromosomes and

begin to move the chromosomes

Kinetochores are protein complexes that assemble

on sections of DNA at centromeres

At metaphase, the centromeres of all the

chromosomes are at the metaphase plate, an

imaginary structure at the midway point between

the spindle’s two poles

Video: Mitosis Spindle

Figure 9.8

Metaphase plate(imaginary)

Chromosomes

Kinetochoremicrotubules

Kineto-chores

Sisterchromatids

Centrosome

Overlappingnonkinetochoremicrotubules

Centrosome

Microtubules

Figure 9.8a

Chromosomes

Centrosome

Microtubules

Figure 9.8b

Kinetochoremicrotubules

Kinetochores

In anaphase, sister chromatids separate and move

along the kinetochore microtubules toward opposite

ends of the cell

The microtubules shorten by depolymerizing at their

kinetochore ends

Chromosomes are also “reeled in” by motor proteins

at spindle poles, and microtubules depolymerize

after they pass by the motor proteins

Figure 9.9

Kinetochore

Experiment

Spindlepole

Results

Kinetochore

Conclusion

Tubulinsubunits

Chromosome

Motorprotein

Chromosomemovement

Microtubule

Figure 9.9a

Kinetochore

Experiment

Spindlepole

Figure 9.9b

Results

Kinetochore

Conclusion

Tubulinsubunits

Chromosome

Motorprotein

Chromosomemovement

Microtubule

Nonkinetochore microtubules from opposite poles

overlap and push against each other, elongating

the cell

At the end of anaphase, duplicate groups of

chromosomes have arrived at opposite ends of the

elongated parent cell

Cytokinesis begins during anaphase or telophase

and the spindle eventually disassembles

Cytokinesis: A Closer Look

In animal cells, cytokinesis occurs by a process

known as cleavage, forming a cleavage furrow

In plant cells, a cell plate forms during cytokinesis

Figure 9.10

(a) Cleavage of an animal cell (SEM)

New cell wall

Contractile ring ofmicrofilaments

Cleavage furrow

Daughter cells

Cell plate

Wall of parentcell

Vesiclesformingcell plate

(b) Cell plate formation in a plant cell (TEM)

Figure 9.10a

(a) Cleavage of an animal cell (SEM)

Contractile ring ofmicrofilaments

Cleavage furrow

Daughter cells

Figure 9.10aa

Cleavage furrow 100 m

Figure 9.10b

New cell wall

Daughter cells

Cell plate

Wall of parentcell

(b) Cell plate formation in a plant cell (TEM)

Figure 9.10ba

Wall of parentcell

Figure 9.11

Nucleus

Telophase

Nucleolus

Chromosomescondensing Chromosomes

Prometaphase

Cell plate

Prophase

AnaphaseMetaphase

Figure 9.11a

Nucleus

Nucleolus

Chromosomescondensing

Prophase1

Figure 9.11b

10 m2 Prometaphase

Chromosomes

Figure 9.11c

10 m3 Metaphase

Figure 9.11d

10 m4 Anaphase

Figure 9.11e

10 m5 Telophase

Cell plate

Binary Fission in Bacteria

Prokaryotes (bacteria and archaea) reproduce by a

type of cell division called binary fission

In E. coli, the single chromosome replicates,

beginning at the origin of replication

The two daughter chromosomes actively move apart

while the cell elongates

The plasma membrane pinches inward, dividing the

cell into two

Figure 9.12-1

Origin ofreplication

Two copiesof origin

Bacterialchromosome

Plasmamembrane

Cell wall

E. coli cell

Chromosomereplicationbegins.

Figure 9.12-2

Two copiesof origin

Bacterialchromosome

Plasmamembrane

Cell wall

E. coli cell

Origin Origin

2 One copy of theorigin is now ateach end of thecell.

Figure 9.12-3

Two copiesof origin

Bacterialchromosome

Plasmamembrane

Cell wall

E. coli cell

Origin Origin

One copy of theorigin is now ateach end of thecell.

Replicationfinishes.

Figure 9.12-4

Two copiesof origin

Bacterialchromosome

Plasmamembrane

Cell wall

E. coli cell

Origin Origin

One copy of theorigin is now ateach end of thecell.

Replicationfinishes.

Two daughtercells result.

The Evolution of Mitosis

Since prokaryotes evolved before eukaryotes,

mitosis probably evolved from binary fission

Certain protists (dinoflagellates, diatoms, and some

yeasts) exhibit types of cell division that seem

intermediate between binary fission and mitosis

Figure 9.13Chromosomes

Intact nuclearenvelope

Microtubules

Intact nuclearenvelope

(a) Dinoflagellates

(b) Diatoms and some yeasts

Concept 9.3: The eukaryotic cell cycle is regulated by a molecular control system

The frequency of cell division varies with the type

of cell

These differences result from regulation at the

molecular level

Cancer cells manage to escape the usual controls

on the cell cycle

Evidence for Cytoplasmic Signals

The cell cycle is driven by specific signaling

molecules present in the cytoplasm

Some evidence for this hypothesis comes from

experiments with cultured mammalian cells

Cells at different phases of the cell cycle were fused

to form a single cell with two nuclei at different

stages

Cytoplasmic signals from one of the cells could

cause the nucleus from the second cell to enter the

“wrong” stage of the cell cycle

Figure 9.14

G1 nucleusimmediately enteredS phase and DNAwas synthesized.

Experiment

Experiment 1 Experiment 2

Results

G1 nucleus beganmitosis withoutchromosomeduplication.

Conclusion Molecules present in the cytoplasmcontrol the progression to S and M phases.

Checkpoints of the Cell Cycle Control System

The sequential events of the cell cycle are directed

by a distinct cell cycle control system, which is

similar to a timing device of a washing machine

The cell cycle control system is regulated by both

internal and external controls

The clock has specific checkpoints where the cell

cycle stops until a go-ahead signal is received

Figure 9.15

M checkpoint

G1 checkpoint

G2 checkpoint

Controlsystem

For many cells, the G1 checkpoint seems to be the

most important

If a cell receives a go-ahead signal at the G1

checkpoint, it will usually complete the S, G2, and

M phases and divide

If the cell does not receive the go-ahead signal, it

will exit the cycle, switching into a nondividing state

called the G0 phase

Figure 9.16

M checkpoint

G1 checkpoint

Without go-ahead signal,cell enters G0.

With go-ahead signal,cell continues cell cycle.

(a) G1 checkpoint

Prometaphase

Without full chromosomeattachment, stop signal isreceived.

(b) M checkpoint

checkpoint

Metaphase

Anaphase

With full chromosomeattachment, go-ahead signalis received.

Figure 9.16a

G1 checkpoint

Without go-ahead signal,cell enters G0.

With go-ahead signal,cell continues cell cycle.

(a) G1 checkpoint

Figure 9.16b

M checkpoint

Prometaphase

Without full chromosomeattachment, stop signal isreceived.

(b) M checkpoint

checkpoint

Metaphase

Anaphase

With full chromosomeattachment, go-ahead signalis received.

The cell cycle is regulated by a set of regulatory

proteins and protein complexes including kinases

and proteins called cyclins

An example of an internal signal occurs at the M

phase checkpoint

In this case, anaphase does not begin if any

kinetochores remain unattached to spindle

microtubules

Attachment of all of the kinetochores activates a

regulatory complex, which then activates the enzyme

separase

Separase allows sister chromatids to separate,

triggering the onset of anaphase

Some external signals are growth factors, proteins

released by certain cells that stimulate other cells to

divide

For example, platelet-derived growth factor (PDGF)

stimulates the division of human fibroblast cells in

culture

Figure 9.17-1

1 A sample ofhuman connectivetissue is cutup into smallpieces.

Petridish

Scalpels

Figure 9.17-2

2 Enzymes digestthe extracellularmatrix, resultingin a suspension offree fibroblasts.

Petridish

Scalpels

Figure 9.17-3

Enzymes digestthe extracellularmatrix, resultingin a suspension offree fibroblasts.

Cells are transferredto culture vessels.

Petridish

Scalpels

4 PDGF is added tohalf the vessels.

Figure 9.17-4

Enzymes digestthe extracellularmatrix, resultingin a suspension offree fibroblasts.

Cells are transferredto culture vessels. PDGF is added to

half the vessels.

Without PDGF With PDGFCultured fibroblasts(SEM) 10 m

Petridish

Scalpels

Figure 9.17a

Cultured fibroblasts(SEM) 10 m

Another example of external signals is density-

dependent inhibition, in which crowded cells stop

dividing

Most animal cells also exhibit anchorage

dependence, in which they must be attached to a

substratum in order to divide

Cancer cells exhibit neither density-dependent

inhibition nor anchorage dependence

Figure 9.18

Anchorage dependence: cellsrequire a surface for division

Density-dependent inhibition:cells divide to fill a gap andthen stop

Density-dependent inhibition:cells form a single layer

(a) Normal mammalian cells (b) Cancer cells

Figure 9.18a

(a) Normal mammalian cells

Figure 9.18b

(b) Cancer cells

Loss of Cell Cycle Controls in Cancer Cells

Cancer cells do not respond to signals that normally

regulate the cell cycle

Cancer cells may not need growth factors to grow

and divide

They may make their own growth factor

They may convey a growth factor’s signal without the

presence of the growth factor

They may have an abnormal cell cycle control system

A normal cell is converted to a cancerous cell by a

process called transformation

Cancer cells that are not eliminated by the immune

system form tumors, masses of abnormal cells within

otherwise normal tissue

If abnormal cells remain only at the original site, the

lump is called a benign tumor

Malignant tumors invade surrounding tissues and

can metastasize, exporting cancer cells to other

parts of the body, where they may form additional

Figure 9.19

1 A tumor growsfrom a singlecancer cell.

Cancer cellsinvadeneighboringtissue.

Cancer cells spreadthrough lymph andblood vessels toother parts of the body.

A small percentageof cancer cells maymetastasize toanother part of the body.

Breast cancer cell(colorized SEM)

Lymphvessel

Bloodvessel

Cancercell

Metastatictumor

Glandulartissue

Figure 9.19a

A tumor growsfrom a singlecancer cell.

Cancer cellsinvadeneighboringtissue.

Cancer cells spreadthrough lymph andblood vessels toother parts of the body.

Glandulartissue

Figure 9.19b

43 Cancer cells spreadthrough lymph andblood vessels toother parts of the body.

A small percentageof cancer cells maymetastasize toanother part of the body.

Lymphvessel

Bloodvessel

Cancercell

Metastatictumor

Figure 9.19c

Breast cancer cell(colorized SEM)

Recent advances in understanding the cell cycle

and cell cycle signaling have led to advances in

cancer treatment

Medical treatments for cancer are becoming more

“personalized” to an individual patient’s tumor

One of the big lessons in cancer research is how

complex cancer is

Figure 9.UN01

Control Treated

A B CA B C

Amount of fluorescence per cell (fluorescence units)

0 200 400 600

Figure 9.UN02

G2Mitosis

Telophase andCytokinesis

Cytokinesis

MITOTIC (M) PHASE

Anaphase

Metaphase

Prometaphase

Prophase

Figure 9.UN03

The Cell Cycle - AP Biology · The cell cycle is driven by specific signaling molecules present in...

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