Chapter 10 How Cell Divide Copyright © The McGraw-Hill Companies, Inc. Permission required for...

Chapter 10

How Cell Divide

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Bacterial Cell Division• Bacteria divide by binary fission

– No sexual life cycle– Reproduction is clonal

• Bacterial genome made up of single, circular chromosome tightly packed in the cell at the nucleoid region.

• Replication begins at the origin of replication and proceeds in two directions to site of termination

• New chromosomes are partitioned to opposite ends of the cell

• Septum forms to divide the cell into 2 cells

Prior to cell division,the bacterial DNAmolecule replicates.The replication of thedouble-stranded,Circular DNA mole-cule that constitutesthe genome of abacterium begins at aspecific site, calledthe origin of replica-tion (green area).

The replicationenzymes move outin both directionsfrom that site andmake copies of eachstrand in the DNAduplex. The enzymes continue until they meet at another specific site, the terminus of replication (red area).

As the DNA isreplicated, the cellelongates, and theDNA is partitioned in the cell such that the origins are at the ¼ and ¾ positions in the cell and the termini are oriented toward the middle of the cell.

1.

2.

3.

Bacterial cell

Bacterial chromosome:Double-stranded DNA

Origin ofreplication


5.

Septation then begins, in which new membrane and cell wall materialbegin to grow and form a septum at approximately the midpoint of the cell. A protein molecule called FtsZ (orange dots) facilitates this process.

When the septum is complete, the cell pinchesin two, and two daughter cells are formed,each containing a bacterial DNA molecule.

4.

Septum


Eukaryotic Chromosomes

• Every species has a different number of chromosomes

• Humans have 46 chromosomes in 23 nearly identical pairs– Additional/missing

chromosomes usually fatal with some exceptions (Chapter 13)

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© Biophoto Associates/Photo Researchers, Inc.

Chromosomes Composition• composed of chromatin – complex of DNA and

protein• DNA is one long continuous double-stranded

polynucleotides• Typical human chromosome is 140 million nucleotides long

• RNA is also associated with chromosomes during RNA synthesis

Chromosome Structure• Nucleosome

– complex of DNA and histone proteins Promote and guide coiling of DNA

– DNA duplex coiled around 8 histone proteins every 200 nucleotides

– Histones are positively charged and strongly attracted to negatively charged phosphate groups of DNA


Mitotic Chromosome

Chromatin loop

Solenoid

Scaffoldprotein

Scaffold protein

Chromatin LoopRosettes of Chromatin Loops

Levels of Eukaryotic Chromosomal Organization

Chromosome Karyotypes• Particular array of chromosomes in an individual organism

is called karyotype.– Arranged according to size, staining properties, location of

centromere, etc.• Humans are diploid (2n)

– 2 complete sets of chromosomes– 46 total chromosomes

• Haploid (n) – 1 set of chromosomes– 23 in humans

• Only found in egg and sperm

• Pair of chromosomes are homologous– Each one is a homologue

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© CNRI/Photo Researchers, Inc.

A Human Karyotype

Chromosome Replication

• Prior to replication, each chromosome composed of a single DNA molecule

• After replication, each chromosome composed of 2 identical DNA molecules– Held together by cohesin proteins

• Visible as 2 strands held together as chromosome becomes more condensed– One chromosome composed of 2 sister

chromatids

Eukaryotic Cell Cycle1. G1 (gap phase 1)

– Primary growth phase, longest phase– In G, cell is being cell

2. S (synthesis)– Replication of DNA

3. G2 (gap phase 2)– Organelles replicate, microtubules

organize4. M (mitosis)

– Subdivided into 5 phases5. C (cytokinesis)

– Separation of 2 new cells

Interphase

Duration of Cell Cycle• Time it takes to complete a cell cycle varies greatly

• Depends on cell type• The shortest known animal cell cycles occur in fruit fly embryos = 8 minutes

• Mature cells take longer than those embryonic tissue to grow– Typical mammalian cell takes 24 hours– Liver cell takes more than a year

• Growth occurs during G1, G2, and S phases– M phase takes only about an hour

• Most variation in length of G1

– Resting phase G0 – cells spend more or less time here

Duration of Cell Cycle• Most variation in the length of the cell cycle between

organisms or cell types occurs in G1

– Cells often pause in G1before DNA replication and enter a resting state called G0

– Resting phase G0 – cells spend more or less time here before resuming cell division.

– Most of cells in animal’s body at any given time are in G0 phase, they may be like that for days, months or years (depending on cell type)

• nerve cells remain there permanently– That is why damage to nerve cells is permanent, they will never enter into replication

– Liver cells can resume G1 phase in response to factors released during injury

• Cell Cycle (2 stages)1. Interphase (G1, S, G2)2. Mitosis (prophase,

metaphase, anaphase, telophase)

Interphase: Preparation for Mitosis

• G1, S, and G2 phases– G1 – cells undergo major portion of growth– S – synthesis of new DNA strands

• replicate DNA produce two sister chromatids attached at the centromere

– G2 – chromosomes coil more tightly using motor proteins; centrioles replicate; organelles replicate

Centromere – point of constrictionKinetochore – attachment site for microtubules to pull chromosomes apart during mitosis

Mitosis is divided into phases:• Prophase

• Prometaphase• Metaphase• Anaphase• Telophase

Prophase• Individual condensed chromosomes first

become visible with the light microscope• Spindle apparatus assembles

– 2 centrioles move to opposite poles forming spindle apparatus (no centrioles in plants)

• Nuclear envelope breaks down

• Chromosomes condense and become visible

• Chromosomes appear as two sister chromatids held together at the centromere

• Nuclear envelope breaks down

Mitotic spindlebeginning to form

Condensedchromosomes

Prophase

Prometaphase• Transition occurs after disassembly of nuclear

envelope• Microtubule attachment

– Each sister chromatid connected to opposite poles• Chromosomes begin to move to center of cell –

congression – Assembly and disassembly of microtubules– Motor proteins at kinetochores

• Chromosomes attach to microtubules at the kinetochores

• Each chromosome is oriented such that the kinetochores of sister chromatids are attached to microtubules from opposite poles.

•

Centromere andkinetochore

Mitoticspindle

Prometaphase

• All chromosomes are aligned at equator of the cell, called the metaphase plate

Polar microtubule

Chromosomesaligned on

metaphase plateKinetochoremicrotubule

Metaphase

Anaphase• Begins when centromeres split• Key event is removal of cohesin proteins

from all chromosomes• Sister chromatids pulled to opposite poles

Chromosomes

• Proteins holding centromeres of sister chromatids are degraded, freeing individual chromosomes

• Chromosomes are pulled to opposite poles (anaphase A) Kinetochore

microtubule

Polarmicrotubule

Anaphase

Telophase• Spindle apparatus disassembles• Nuclear envelope forms around each set

of chromosomes• Chromosomes begin to uncoil• Nucleolus reappears in each new nucleus

Polar microtubule

Nucleus reforming

• Chromosomes are clustered at opposite poles and decondense

• Nuclear envelopes re-form around chromosomes

• Golgi complex and ER re-form

Kinetochoremicrotubule

Telophase

Cytokinesis• Cleavage of the cell into equal halves• Animal cells – constriction of actin

filaments produces a cleavage furrow• Plant cells – cell plate forms between the

nuclei• Fungi and some protists – nuclear

membrane does not dissolve; mitosis occurs within the nucleus; division of the nucleus occurs with cytokinesis

• At the end of mitosis, you get 2 daughter cells that have the exact same chromosomes as the original parent cell

33

Control of the Cell Cycle• Cell cycle as to be regulated• Do not want uncontrolled cell division, this leads to

CANCER!• Cell must receive the proper signals to move into mitosis

and there are checkpoints (to check the proper signal, to check the integrity of the DNA, to check that one of each replicated chromosome moved correctly, etc)

3 Checkpoints1. G1/S checkpoint

– Cell “decides” whether or not to divide– Primary point for external signal influence; did it

receive signal for replication?2. G2/M checkpoint

– Cell makes a commitment to mitosis– Assesses success of DNA replication – are there

mistakes?– Can stall the cycle if DNA has not been accurately

replicated.3. Late metaphase (spindle) checkpoint

– Cell ensures that all chromosomes are attached to the spindle

Cyclin-dependent kinases (Cdks)• Progress through cell cycle depends on cyclin dependent kinases

(Cdks)• Cdks are not active by themselves

– Have to bind to cyclin to be activated • Cyclins can be produced in response to stimulus, or can be

inhibited so it can’t bind to kinase• If cyclin binds to Cdk it is now cyclin-Cdk

– This cyclin-Cdk can now transfer phosphate group from ATP to target protein

– That target protein (like RB) will then be involved in moving cell past the checkpoint

» Phosphorylation of the RB inhibits the RB and allows cell to move past the checkpoint

• Cdk – cyclin complex– Also called mitosis-promoting factor (MPF)

• Activity of Cdk is also controlled by the pattern of phosphorylation– Phosphorylation at one site (red) inactivates Cdk– Phosphorylation at another site (green) activates Cdk

Cyclin-dependent kinase(Cdk)

Cyclin

P

P

The Action of MPF(mitosis promoting factor or cyclin-Cdk)

• Damage to DNA acts through a complex pathway to tip the balance toward the inhibitory phosphorylation of MPF

• Example – p21– p21 is a protein that is made in response to DNA damage due to

radiation– If p21 is present, it binds the G1-S Cdk, preventing activation by the

cyclin– So the cell cycle stops until damage is repaired or until the cell is killed

Growth factors• Act by triggering intracellular signaling systems• Platelet-derived growth factor (PDGF) one of the first

growth factors to be identified• PDGF receptor is a receptor tyrosine kinase (RTK)

that initiates a MAP kinase cascade to stimulate cell division

• If you cut yourself and bleed, platelets gather to make clot, release protein (PDGF, growth factor) that stimulates adjacent cells to divide and heal wound

• Growth factors can override cellular controls that otherwise inhibit cell division

A cascade of eventsthat lead to certaingenes being transcribed and translated (in other words, genes willbe used to cause the cell to respond to thestimulus)

CancerUnrestrained, uncontrolled growth of cells•Failure of cell cycle control•Two kinds of genes can disturb the cell cycle when they are mutated

• Tumor-suppressor genes• Proto-oncogenes

Tumor-suppressor genes• p53 plays a key role in G1 checkpoint• p53 protein monitors integrity of DNA

– If DNA damaged, cell division halted and repair enzymes stimulated

– If DNA damage is irreparable, p53 directs cell to kill itself

• Prevent the development of mutated cells containing mutations

• p53 gene is absent or damaged in many cancerous cells

Tumor-suppressor genes• First tumor-suppressor identified was the retinoblastoma susceptibility

gene (Rb)– Predisposes individuals for a rare form of cancer that affects the retina

of the eye• Inheriting a single mutant copy of Rb means the individual has only one

“good” copy left– During the hundreds of thousands of divisions that occur to produce the

retina, any error that damages the remaining good copy leads to a cancerous cell

– Single cancerous cell in the retina then leads to the formation of a retinoblastoma tumor

Proto-oncogenes• Proto-oncogenes are normal cellular genes

that become oncogenes when mutated– Oncogenes can cause cancer

• Some encode receptors for growth factors– If receptor is mutated in “on” position, cell no longer

depends on growth factors, it will just continue to divide on its own

– The cell will then replicate uncontrollably

Proto-oncogenes

Growth factor receptor: more per cell in many breast cancers.Ras protein: activated by mutations in 20–30% of all cancers.Src kinase: activated by mutations in 2–5% of all cancers.

Tumor-suppressor Genes

Rb protein: mutated in 40% of all cancers.

p53 protein: mutated in 50% of all cancers.

Cell cyclecheckpoints

Rasprotein

Rbprotein p53

protein

Srckinase

Mammalian cell

Nucleus

Cytoplasm

Key Proteins Associated with Human Cancers

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