cell cycle

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

PowerPoint Lectures for Biology, Seventh Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero

Chapter 12Chapter 12Chapter 12Chapter 12

The Cell CycleThe Cell Cycle


Introduction: Key Roles of Cell DivisionIntroduction: Key Roles of Cell Division

• The ability of organisms to reproduce their kind is one characteristic that best distinguishes living things from nonliving matter.

• The continuity of life from one cell to another is based on the reproduction of cells via cell division.

• This division process occurs as part of the cell cycle, the life of a cell from its origin in the division of a parent cell until its own division into two.


Cell division requires coordinated division of chromosomes (mitosis) …..

…… and division of the cytoplasm (cytokinesis).


Introduction: Key Roles of Cell DivisionIntroduction: Key Roles of Cell Division

• In unicellular organisms, division of one cell reproduces the entire organism i.e. cloning

• Multicellular organisms depend on cell division for:

– Development

– Growth

– Repair

LE 12-2LE 12-2LE 12-2LE 12-2

Reproduction

100 µm

Tissue renewalGrowth and development

20 µm200 µm


Cell division results in genetically Cell division results in genetically identical daughter cellsidentical daughter cells

• Cells duplicate their genetic material before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA

• A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and only then splits into daughter cells


Cellular Organization of the Genetic Cellular Organization of the Genetic MaterialMaterial

• A cell’s endowment of DNA ( genetic information) is called its genome

• DNA molecules in a cell are packaged into units called chromosomes

– Every eukaryotic species has a characteristic number of chromosomes in the nucleus.

– Human somatic cells (body cells) have 46 chromosomes, called the diploid number or 2n

• Human gametes, sperm or egg, have 23 chromosomes, or half the diploid number (n; haploid)


Chromosome AnatomyChromosome Anatomy

•Eukaryotic chromosomes consist of chromatin, a complex of DNA and proteins that condenses during cell division

•In preparation for cell division, DNA is replicated and the chromosomes condense

•Each duplicated chromosome consists of two sister chromatids which contain identical copies of the chromosome’s DNA.

•As they condense, the region where the strands connect shrinks to form a narrow site called the centromere.

LE 12-3LE 12-3LE 12-3LE 12-3

25 µm

1888W. Waldeyer was the first to introducethe term chromosome meaning “colored body”.


• Eukaryotic cell division consists of 2 phases:

– Mitosis (karyokinesis), division of the nucleus

– Cytokinesis, division of the cytoplasm

• Gametes are produced by a variation of cell division called meiosis

• Meiosis yields non-identical daughter cells that have only one set of chromosomes, half as many as the parent cell

Cell DivisionCell Division


M phase alternates with InterphaseM phase alternates with Interphase

• In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis

• To Flemming, it appeared that the cell simply grew larger between one cell division and the next

• Today we know that many critical events occur during this stage in a cell’s life

• Mitosis =Greek for “thread”

http://www.biology.arizona.edu/Cell_bio/tutorials/cell_cycle/MitosisFlash.html


Phases of the Cell CyclePhases of the Cell Cycle

• The cell cycle consists of

– Mitotic (M) phase (mitosis and cytokinesis)

– Interphase (cell growth and copying of chromosomes in preparation for cell division)

• Interphase (about 90% of the cell cycle) can be divided into subphases:

– G1 phase (“first gap”)

– S phase (“synthesis”)

– G2 phase (“second gap”)

http://wps.prenhall.com/wps/media/objects/486/498658/CDA8_1/CDA8_1b/CDA8_1b.htm

Cell Cell CycleCycle

next


Overview: Overview: Phases of MitosisPhases of Mitosis

next

• Mitosis is conventionally divided into five phases:

– Prophase

– Prometaphase

– Metaphase

– Anaphase

– Telophase

• Cytokinesis is well underway by late telophase

http://media.pearsoncmg.com/bc/bc_0media_bio/bioflix/bioflix.htm?c8emitosis

Stages of Mitosis- pics* * Sumanas, Inc. animation - Mitosis

•Prophase - chromatin condenses into chromosomes •Prometaphase -chromosome MT's attach to kinetochores each homolog has 2 chromatids fig 12.6*

•Metaphase - chromosomes align at equator homologs align independently of each other fig 12.6*

•Anaphase - MT attached to kinetochore; chromatids are pulled apart & poles move apart fig12.8*

•Telophase - chromosomes at opposite poles; daughter cells form by cytokinesis onion root tip cells*

next

http://fig.cox.miami.edu/~cmallery/150ss97/emasexual.htm

http://fig.cox.miami.edu/~cmallery/150ss97/emasexual.htm

http://www.sumanasinc.com/webcontent/anisamples/majorsbiology/mitosis.html







Video: Animal Mitosis

Video: Sea Urchin (time lapse)

Animation: Mitosis (All Phases)

Animation: Mitosis Overview

Animation: Late Interphase

Animation: Prophase

Animation: Prometaphase

Animation: Metaphase

Animation: Anaphase

Animation: Telophase

Mitotic Animations and VideosMitotic Animations and Videos

http://media.pearsoncmg.com/bc/bc_campbell_biology_7/mm2/ch12/InstructorResources/medialib_tab_3/2.htm













The Mitotic Spindle: The Mitotic Spindle: A Closer LookA Closer Look

• The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis

• Assembly of spindle microtubules begins in the centrosome or MOC (microtubule organizing center)

• The centrosome, contains a pair of centrioles, replicates, forming two centrosomes; migrate to opposite ends of the cell, as spindle microtubules grow out from them

• An aster (a radial array of short microtubules) extends from each centrosome


• The spindle includes the centrosomes, the spindle microtubules, and the asters

• Some spindle microtubules attach to a structure the kinetochores of chromosomes and move the chromosomes to the metaphase plate


LE 12-7LE 12-7LE 12-7LE 12-7

Microtubules Chromosomes

Sisterchromatids

AsterCentrosome

Metaphaseplate

Kineto-chores

Kinetochoremicrotubules

0.5 µm

Overlappingnonkinetochoremicrotubules

1 µmCentrosome



• In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell

• The microtubules shorten by depolymerizing tubulin subunits at their kinetochore ends


Chromosomemovement

Microtubule Motorprotein

Chromosome

Kinetochore

Tubulinsubunits

What is happening at the kinetochore?What is happening at the kinetochore?

The kinetochore motor proteins detach and reattach to the kinetochore microtubule, this causes the microtubule to shorten (depolymerize)and thus moving the chromosome.


• Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell

• In telophase, genetically identical daughter nuclei form at opposite ends of the cell



Cytokinesis: Cytokinesis: A Closer LookA 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

Activity Animation: Cytokinesis

http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?12&D

LE 12-9aLE 12-9aLE 12-9aLE 12-9a

Cleavage furrow100 µm

Contractile ring ofmicrofilaments

Daughter cells

Cleavage of an animal cell (SEM)

LE 12-9bLE 12-9bLE 12-9bLE 12-9b

1 µm

Daughter cells

Cell plate formation in a plant cell (TEM)

New cell wallCell plate

Wall ofparent cell

Vesiclesformingcell plate

LE 12-10LE 12-10LE 12-10LE 12-10

NucleusCell plateChromosomesNucleolus

Chromatincondensing 10 µm

Prophase. The chromatin is condensing.The nucleolus is beginning to disappear.Although not yet visible in the micrograph, the mitotic spindle is starting to form.

Prometaphase. Wenow see discrete chromosomes; each consists of two identical sister chromatids. Laterin prometaphase, the nuclear envelope will fragment.

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

Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore microtubules shorten.

Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell.


Binary FissionBinary Fission

• Prokaryotes (bacteria and archaea) reproduce by a type of asexual reproduction called binary fission

• In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart

Origin ofreplication

Cell wall

Plasmamembrane

Bacterialchromosome

E. coli cell

Two copiesof origin

Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell.

Binary FissionBinary Fission

LELE 12-11_212-11_2LELE 12-11_212-11_2


Cell wall

Plasmamembrane

Bacterialchromosome

E. coli cell

Two copiesof origin


Replication continues. One copy of the origin is now at each end of the cell.

Origin Origin

LE 12-11_3LE 12-11_3LE 12-11_3LE 12-11_3


Cell wall

Plasmamembrane

Bacterialchromosome

E. coli cell

Two copiesof origin


Replication continues. One copy of the origin is now at each end of the cell.

Origin Origin

Replication finishes. The plasma membrane grows inward, and new cell wall is deposited.

Two daughtercells result.


The Evolution of MitosisThe Evolution of Mitosis

• Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission (or “division in half”)

• Process does not involve mitosis

• Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis.

• Evidence that modern day mitosis evolved from bacterial binary fission lies in the fact that similar bacterial proteins are related to eukaryotic proteins and function to support mitosis.

LE 12-12LE 12-12LE 12-12LE 12-12Bacterialchromosome

Chromosomes

Microtubules

Prokaryotes

Dinoflagellates

Intact nuclearenvelope



Intact nuclearenvelope

Diatoms and yeasts

Centrosome

Most eukaryotes

Fragments ofnuclear envelope


The cell cycle is regulated by a The cell cycle is regulated by a molecular control system at several molecular control system at several pointspoints

• The frequency of cell division varies with the type of cell

• These cell cycle differences result from regulation at the molecular level


Evidence for Cytoplasmic SignalsEvidence for Cytoplasmic Signals

• The cell cycle appears to be driven by specific chemical signals present in the cytoplasm

• Cell fusion experiments identified the existence of a molecular cell cycle switch in cells

• Evidence for this hypothesis comes from 1970’s experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei the hybrid cell is a heterokaryon

• Which nucleus controlled the cell cycle?

The Rao Johnson The Rao Johnson Experiment ExperimentThe Rao Johnson The Rao Johnson

Experiment Experiment Experiment 1 Experiment 2

S

S S

G1 G1M

M M

When a cell in the M phase was fused with a cell in G1, the G1 cell immediately beganmitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Something in M phase induced interphase cells to divide.

When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized. S cells contained something that induced regulation in G1 cells.


Conclusion:Conclusion:

• There are factors that can promote S or M phase. The S phase promoting factor only works on G1 nuclei. The M phase promoter works on everything.

• In 1971 this M phase promoter from the cytoplasm of M phase Xenopus eggs was identified.

• The M phase protein called MPF (maturation promoting factor) induced immature egg cells to enter M phase.


African clawed frogAfrican clawed frog

• Xenopus laevis popular organism due to large oocytes.


Conclusions from Xenopus experimentsConclusions from Xenopus experiments

• MPF induces all eukaryotic cells to undergo mitosis;

• MPF is a dimer, composed of a protein kinase (Cdk-cyclin dependent kinase) and a cyclin

• Cdk is an enzyme that phosphorylates a protein

• Cyclin is a protein that attaches to and activates the Cdk molecule.


• Regulated by "Growth Factors" (GF)- intercellular signals that trigger cells to pass from G1 checkpoint

• MPF - mitotic promoting factor- complex* of two proteins: cdkcdk + + cyclincyclin

• MPF is a kinase enzyme, switches on/off target cell cycle proteins by phosphorylating them..... inactive cycle protein ------------->active-P ATP ADP

• MPF promotes entrance into mitosis from the G2 phase by phosphorylating multiple proteins during mitosis including one that leads to destruction of cyclin itself MPF cdk - a cell division control protein - cyclin dependent kinase; active only when bound to cyclin; cyclin - a protein whose amount varies cyclically*; when in high concentrations*, binds to cdk makes MPF... [cyclin + cdk = MPF].. favors Mitosis GF regulated at critical points... Cell cycle checkpoints*

Control of Cell Division and the Cell CycleControl of Cell Division and the Cell Cycle2001 Nobel prize

http://fig.cox.miami.edu/~cmallery/150/mitosis/c12x15growth-factor.jpg

http://fig.cox.miami.edu/~cmallery/150/mitosis/sf8x15b.jpg



http://fig.cox.miami.edu/~cmallery/150/mitosis/sf8x15a.jpg

http://fig.cox.miami.edu/~cmallery/150/mitosis/control.htm

http://www.nobel.se/medicine/laureates/2001/index.html


The Cell Cycle Control SystemThe 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 clock

• The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received


• For many cells, the G1 checkpoint seems to be the most important one

• 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

The Cell Cycle Control SystemThe Cell Cycle Control System

http://wps.prenhall.com/esm_freeman_biosci_1/7/1948/498717.cw/index.html

LE 12-15LE 12-15LE 12-15LE 12-15

G1

G1 checkpoint

G1

G0

If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.


Stop and Go Signs: Internal and External Signals at the Checkpoints

• An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays 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

LE 12-17LE 12-17

Petriplate

Scalpels

Without PDGF

With PDGF

Without PDGF

With PDGF

10 mm


• 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

Stop and Go Signs: Internal and External Stop and Go Signs: Internal and External Signals at the CheckpointsSignals at the Checkpoints

LE 12-18aLE 12-18aLE 12-18aLE 12-18a

Cells anchor to dish surface anddivide (anchorage dependence).

When cells have formed a completesingle layer, they stop dividing(density-dependent inhibition).

If some cells are scraped away, theremaining cells divide to fill the gap andthen stop (density-dependent inhibition).

25 µmNormal mammalian cells


Cancer cells escape cell cycle controls

• Cancer cells divide excessively and invade other tissues because they are free of the body’s control mechanisms.

– Cancer cells do not stop dividing when growth factors are depleted either because they manufacture their own, have an abnormality in the signaling pathway, or have a problem in the cell cycle control system.

• If and when cancer cells stop dividing, they do so at random points, not at the normal checkpoints in the cell cycle.

LE 12-18bLE 12-18bLE 12-18bLE 12-18b

Cancer cells do not exhibit anchorage dependenceor density-dependent inhibition.

Cancer cells25 µm


Loss of Cell Cycle Controls =Cancer CellsLoss of Cell Cycle Controls =Cancer Cells

• Cancer cells do not respond normally to the body’s control mechanisms

• Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue

• If abnormal cells remain 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 secondary tumors


• Cancer cells may divide indefinitely if they have a continual supply of nutrients.

– In contrast, nearly all mammalian cells divide 20 to 50 times under culture conditions before they stop, age, and die.

– Cancer cells may be “immortal”.

• Cells (HeLa) from a tumor removed from a woman (Henrietta Lacks) in 1951 are still reproducing in culture.

Cancer cells escape cell cycle controls

Cancer cell

Bloodvessel

LymphvesselTumor

Glandulartissue

Metastatictumor

A tumor grows from asingle cancer cell.

Cancer cells invadeneighboring tissue.

Cancer cells spreadthrough lymph andblood vessels toother parts of thebody.

A small percentageof cancer cells maysurvive and establisha new tumor in anotherpart of the body.

Cancer Cancer


PowerPoint Lectures for Biology, Seventh Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero

Chapter 12 Chapter 12 The Cell CycleThe Cell CycleChapter 12 Chapter 12 The Cell CycleThe Cell Cycle

THE END!THE END!

Technology

cell cycle