© 2013 Pearson Education, Inc. Cell Cycle Defines changes from formation of cell until it...

Cell Cycle

• Defines changes from formation of cell until it reproduces

• Includes:– Interphase

• Cell grows and carries out functions

– Cell division (mitotic phase)• Divides into two cells

Interphase

• Period from cell formation to cell division

• Nuclear material called chromatin

• Three subphases:– G1 (gap 1)—vigorous growth and metabolism

• Cells that permanently cease dividing said to be in G0 phase

– S (synthetic)—DNA replication occurs

– G2 (gap 2)—preparation for division

Figure 3.31 The cell cycle.

G1 checkpoint(restriction point)

SGrowth and DNA

synthesis

Growth

Growth and finalpreparations for

divisionM

Prophase

Metaphase

ytokinesisG2 checkpoint

Figure 3.33 Mitosis is the process of nuclear division in which the chromosomes are distributed to two daughter nuclei. (1 of 6)

InterphaseCentrosomes (eachhas 2 centrioles)

Plasmamembrane

Nucleolus

Nuclearenvelope

Chromatin

DNA Replication

• Prior to division cell makes copy of DNA• DNA helices separated into replication

bubbles with replication forks at each end– Each strand acts as template for

complementary strand

• DNA polymerase begins adding nucleotides at RNA primer

• DNA polymerase continues from primer– Synthesizes one leading, one lagging strand

DNA Replication

• DNA polymerase only works in one direction– Leading strand synthesized continuously– Lagging strand synthesized discontinuously

into segments– DNA ligase splices short segments of

discontinuous strand together

DNA Replication

• End result: two identical DNA molecules formed from original– During mitotic cell division one complete copy

given to new cell; one retained in original cell

• Process is called semiconservative replication– Each DNA composed of one old and one new

strand

Figure 3.32 Replication of DNA: summary.

ChromosomeFree nucleotides DNA polymerase Old (parental) strand acts as a

template for synthesis of newstrand

Leadingstrand

Replicationbubble

Laggingstrand

Replicationfork

Enzymes unwindthe double helix andexpose the bases

OldDNA

DNApolymerase

Old (template)strand

Two new strands (leadingand lagging) synthesizedin opposite directions

Adenine Thymine Cytosine Guanine

PLAYPLAY Animation: DNA Replication

DNA Replication

Cell Division

• Meiosis - cell division producing gametes• Mitotic cell division - produces clones

– Essential for body growth and tissue repair– Occurs continuously in some cells• Skin; intestinal lining

– None in most mature cells of nervous tissue, skeletal muscle, and cardiac muscle• Repairs with fibrous tissue

Events Of Cell Division

• Mitosis—division of nucleus– Four stages ensure each cell receives copy of

replicated DNA• Prophase• Metaphase• Anaphase• Telophase

– Cytokinesis—division of cytoplasm-by cleavage furrow

Figure 3.31 The cell cycle.

G1 checkpoint(restriction point)

SGrowth and DNA

synthesis

Growth

Growth and finalpreparations for

divisionM

Prophase

Metaphase

ytokinesisG2 checkpoint

PLAYPLAY Animation: Mitosis

Cell Division

Prophase

• Chromosomes become visible, each with two chromatids joined at centromere

• Centrosomes separate and migrate toward opposite poles

• Mitotic spindles and asters form

Prophase

• Nuclear envelope fragments

• Kinetochore microtubules attach to kinetochore of centromeres and draw them toward equator of cell

• Polar microtubules assist in forcing poles apart

Early ProphaseEarly mitoticspindle

Chromosomeconsisting of twosister chromatids

Centromere

Late Prophase

Kinetochore

Spindle pole Polar microtubuleFragmentsof nuclearenvelope

Kinetochoremicrotubule

Metaphase

• Centromeres of chromosomes aligned at equator

• Plane midway between poles called metaphase plate

Metaphase

Metaphaseplate

Spindle

Anaphase

• Shortest phase

• Centromeres of chromosomes split simultaneously—each chromatid becomes a chromosome

• Chromosomes (V shaped) pulled toward poles by motor proteins of kinetochores

• Polar microtubules continue forcing poles apart

Anaphase

Daughterchromosomes

Telophase

• Begins when chromosome movement stops

• Two sets of chromosomes uncoil to form chromatin

• New nuclear membrane forms around each chromatin mass

• Nucleoli reappear

• Spindle disappears

Cytokinesis

• Begins during late anaphase

• Ring of actin microfilaments contracts to form cleavage furrow

• Two daughter cells pinched apart, each containing nucleus identical to original

Telophase CytokinesisNuclearenvelopeforming

Nucleolus forming Contractilering atcleavagefurrow

Control of Cell Division

• "Go" signals:– Critical volume of cell when area of

membrane inadequate for exchange– Chemicals (e.g., growth factors, hormones)– Availability of space–contact inhibition

• To replicate DNA and enter mitosis requires– Cyclins–regulatory proteins

• Accumulate during interphase

– Cdks (Cyclin-dependent kinases)–bind to cyclins activated

• Enzyme cascades prepare cell for division

– Cyclins destroyed after mitotic cell division

• "Go" signals– G1 checkpoints (restriction point) most

important• If doesn't pass G0–no further division

– Late in G2 MPF (M-phase promoting factor) required to enter M phase

• "Other Controls" signals– Repressor genes inhibit cell division

• E.g., P53 gene

• DNA is master blueprint for protein synthesis

• Gene - segment of DNA with blueprint for one polypeptide

• Triplets (three sequential DNA nitrogen bases) form genetic library– Bases in DNA are A, G, T, and C– Each triplet specifies coding for number, kind,

and order of amino acids in polypeptide

PLAYPLAY Animation: DNA and RNA

Protein Synthesis

• Genes composed of exons and introns– Exons code for amino acids– Introns–noncoding segments

• Role of RNA– DNA decoding mechanism and messenger– Three types–all formed on DNA in nucleus

• Messenger RNA (mRNA); ribosomal RNA (rRNA); transfer RNA (tRNA)

• RNA differs from DNA– Uracil is substituted for thymine

Roles of the Three Main Types of RNA

• Messenger RNA (mRNA)– Carries instructions for building a polypeptide,

from gene in DNA to ribosomes in cytoplasm

• Ribosomal RNA (rRNA)– Structural component of ribosomes that, along

with tRNA, helps translate message from mRNA

• Transfer RNAs (tRNAs)– Bind to amino acids and pair with bases of

codons of mRNA at ribosome to begin process of protein synthesis

Figure 3.34 Simplified scheme of information flow from the DNA gene to mRNA to protein structure during transcription and translation.

RNA Processing Pre-mRNA

DNATranscription

Polypeptide

Ribosome

Nuclearpores

Translation

Nuclearenvelope

Protein Synthesis

• Occurs in two steps– Transcription

• DNA information coded in mRNA

– Translation• mRNA decoded to assemble polypeptides

Transcription

• Transfers DNA gene base sequence to complementary base sequence of mRNA

• Transcription factors–gene activators– Loosen histones from DNA in area to be

transcribed– Bind to promoter-DNA sequence specifying

start site of gene on template strand– Mediate binding of RNA polymerase (enzyme

synthesizing mRNA) to promoter

Transcription

• Three phases– Initiation

• RNA polymerase separates DNA strands

– Elongation• RNA polymerase adds complementary nucleotides

– Termination• Termination signal indicates "stop"

Processing of mRNA

• mRNA edited and processed before translation– Introns removed by spliceosomes– mRNA complex proteins associate to guide

export, ensure accuracy for translation

Figure 3.35 Overview of stages of transcription.

The DNA-RNA hybrid: At any given moment, 16–18 base pairs ofDNA are unwound and the most recently made RNA is still bound to DNA. This small region is called the DNA-RNA hybrid.

RNApolymerase

Unwindingof DNA

Coding strand of DNA

TemplatestrandmRNA

DNA-RNA hybrid region

Direction oftranscription

Rewinding of DNA

RNA nucleotides

RNA polymerase

Promoterregion

Template strand Termination

signal

DNACoding strand

mRNA Template strand

mRNA transcript

Completed mRNA transcript

RNA polymerase

Termination: mRNA synthesis ends when the termination signal is reached. RNA polymerase and the completed mRNA transcript are released.

Initiation: With the help of transcription factors, RNA polymerase binds to the promoter, pries apart the two DNA strands, and initiates mRNA synthesis at the start point on the template strand.

Elongation: As the RNA polymerase moves along the template strand, elongating the mRNA transcript one base at a time, it unwinds the DNA double helix before it and rewinds the double helix behind it.

Figure 3.35 Overview of stages of transcription.RNA polymerase

Promoterregion

signal

Coding strand

Figure 3.35 Overview of stages of transcription.RNA polymerase

Promoterregion

signal

Coding strand

RNApolymerase

Unwindingof DNA

TemplatestrandmRNA

Rewinding of DNA

RNA nucleotides

RNA polymerase

Promoterregion

signal

mRNA transcript

Coding strand

RNApolymerase

Unwindingof DNA

TemplatestrandmRNA

Rewinding of DNA

RNA nucleotides

RNA polymerase

Promoterregion

signal

mRNA transcript

Completed mRNA transcript

RNA polymerase

Termination: mRNA synthesis ends when the termination signal is reached. RNA polymerase and the completed mRNA transcript are released.

Coding strand

Translation

• Converts base sequence of nucleic acids into amino acid sequence of proteins

• Involves mRNAs, tRNAs, and rRNAs

Genetic Code

• Each three-base sequence on DNA (triplet) represented by codon– Codon—complementary three-base

sequence on mRNA– Some amino acids represented by more than

one codon

SECOND BASE

Tyr Cys

Asn Ser

CGCLeu

CCCPro

Met orStart

GlyAla

Figure 3.36 The genetic code.

Role of tRNA

• 45 different types• Binds specific amino acid at one end

(stem) • Anticodon at other end (head) binds

mRNA codon at ribosome by hydrogen bonds– E.g., if codon = AUA, anticodon = UAU

• Ribosome coordinates coupling of mRNA and tRNA; contains three sites– Aminoacyl site; peptidyl site; exit site

Sequence of Events in Translation

• Three phases that require ATP, protein factors, and enzymes– Initiation– Elongation– Termination

Translation: Initiation

• Small ribosomal subunit binds to initiator tRNA and mRNA to be decoded; scans for start codon

• Large and small ribosomal units attach, forming functional ribosome

• At end of initiation– tRNA in P site; A site vacant

Translation: Elongation

• Three steps– Codon recognition

• tRNA binds complementary codon in A site

– Peptide bond formation• Amino acid of tRNA in P site bonded to amino acid

of tRNA in A site

– Translocation• tRNAs move one position–A P; P E

Translation: Elongation

• New amino acids added by other tRNAs as ribosome moves along mRNA

• Initial portion of mRNA can be "read" by additional ribosomes– Polyribosome

• multiple ribosome-mRNA complex

– Produces multiple copies of same protein

Figure 3.38 Polyribosome arrays.

Growing polypeptides Completedpolypeptide

Incomingribosomalsubunits

PolyribosomeStart of mRNA End of

Each polyribosome consists of one strand of mRNAbeing read by several ribosomes simultaneously. In thisdiagram, the mRNA is moving to the left and the “oldest”functional ribosome is farthest to the right.

This transmission electron micrograph shows a large polyribosome (400,0003).

Ribosomes

Translation: Termination

• When stop codon (UGA, UAA, UAG) enters A site– Signals end of translation– Protein release factor binds to stop codon

water added to chain release of polypeptide chain; separation of ribosome subunits; degradation of mRNA

– Protein processed into functional 3-D structure

Figure 3.37 Translation is the process in which genetic information carried by an mRNA is decoded in theribosome to form a particular polypeptide.

Elongation. Amino acids are added one ata time to the growing peptide chain via aprocess that has three repeating steps.

Amino acidcorrespondingto anticodon

Templatestrand of DNA

Pre-mRNA

Nucleus (siteof transcription)

The correct amino acid is attached to each species of tRNA by a synthetase enzyme. Ile

tRNAanticodon

Polypeptide

IlePro

ComplementarymRNA codon

New peptidebond

ReleasedtRNA

ProLeu

Peptide bondformation. The growingpolypeptide bound to thetRNA at the P site istransferred to the aminoacid carried by the tRNAin the A site, and a newpeptide bond is formed.

2c Translocation. As theentire ribosome translocates, itshifts by one codon along themRNA:• The unloaded tRNA in the P site is moved to the E site and then released.• The tRNA in the A site moves to the P site.• The next codon to be translated is now in the empty A site ready for step 2a again.

Direction ofribosome movement

PolypeptideRelease factor

Stop codon

Termination. When a stop codon (UGA,UAA, or UAG) arrives at the A site, elongationends. Release of the newly made polypeptideis triggered by a release factor and theribosomal subunits separate, releasing themRNA.

Codon recognition.The anticodon of anincoming tRNA binds withthe complementary mRNAcodon (A to U and C to G)in the A site of theribosome.

Smallribosomalsubunit

Start codon

Initiation. Initiation occurswhen four components combine:• A small ribosomal subunit• An initiator tRNA that carries the amino acid methionine• The mRNA• A large ribosomal subunit Once this is accomplished, the nextphase, elongation, begins.

Initiator tRNAbearing anticodon

Aminoacyl-tRNAsynthetaseMet

Cytosol (siteof translation)

Newly made (andedited) mRNAleaves nucleus andtravels to a free orattached ribosomefor decoding.

Methionine(amino acid)

Largeribosomalsubunit

APEGGC

GAUGAUACC CUA

ACCGCU CUC

ACUGGG UGACCU

GAUACC CUA

Pre-mRNA

The correct amino acid is attached to each species of tRNA by a synthetase enzyme.

Aminoacyl-tRNAsynthetase

Methionine(amino acid)Newly made

(and edited)mRNA leavesnucleus andtravels to a freeor attachedribosome fordecoding.

Start codon

Initiation. Initiation occurswhen four components combine:• A small ribosomal subunit• An initiator tRNA that carries the amino acid methionine• The mRNA• A large ribosomal subunit Once this is accomplished, the next phase, elongation, begins.

1U A C

Elongation. Amino acids areadded one at a time to thegrowing peptide chain via a processthat has three repeating steps.

tRNAanticodon

Codon recognition.The anticodon of anincoming tRNA binds withthe complementary mRNAcodon (A to U and C to G) inthe A site of the ribosome.

APEGGC

GAUACC CUA

Polypeptide

New peptidebond

IlePro

GAUA CC CUAGGGC AU

Peptide bondformation. The growingpolypeptide bound to thetRNA at the P site istransferred to the amino acid carried by the tRNA in the A site, and a new peptide bondis formed.

ReleasedtRNA

E P AG AU

C CG CUA CUC

GGC LeuProIle

Translocation. As the entire ribosome translocates, it shifts by one codon along the mRNA:• The unloaded tRNA in the P site is moved to the E site and then released.• The tRNA in the A site moves to the P site.• The next codon to be translated is now in the empty A site ready for step 2a again.

Direction of ribosome movement

Release factor

Stop codon

G GGU GACC

Termination. When a stop codon (UGA,UAA, or UAG) arrives at the A site, elongation ends. Release of the newly made polypeptide is triggered by a release factor and the ribosomal subunits separate, releasing the mRNA.

Stop codon

G GGU GACC

Elongation. Amino acids are added one ata time to the growing peptide chain via aprocess that has three repeating steps.

Pre-mRNA

The correct amino acid is attached to each species of tRNA by a synthetase enzyme. Ile

tRNAanticodon

Polypeptide

IlePro

New peptidebond

ReleasedtRNA

ProLeu

Peptide bondformation. The growingpolypeptide bound to thetRNA at the P site istransferred to the aminoacid carried by the tRNAin the A site, and a newpeptide bond is formed.

2c Translocation. As theentire ribosome translocates, itshifts by one codon along themRNA:• The unloaded tRNA in the P site is moved to the E site and then released.• The tRNA in the A site moves to the P site.• The next codon to be translated is now in the empty A site ready for step 2a again.

Direction ofribosome movement

Stop codon

Codon recognition.The anticodon of anincoming tRNA binds withthe complementary mRNAcodon (A to U and C to G)in the A site of theribosome.

Start codon

Initiation. Initiation occurswhen four components combine:• A small ribosomal subunit• An initiator tRNA that carries the amino acid methionine• The mRNA• A large ribosomal subunit Once this is accomplished, the nextphase, elongation, begins.

Aminoacyl-tRNAsynthetaseMet

Newly made (andedited) mRNAleaves nucleus andtravels to a free orattached ribosomefor decoding.

Methionine(amino acid)

APEGGC

GAUGAUACC CUA

ACCGCU CUC

ACUGGG UGACCU

GAUACC CUA

Role of Rough ER in Protein Synthesis

• mRNA–ribosome complex directed to rough ER by signal-recognition particle (SRP)

• Forming protein enters ER

• Sugar groups may be added to protein, and its shape may be altered

• Protein enclosed in vesicle for transport to Golgi apparatus

Figure 3.39 Rough ER processing of proteins. Slide 1

The SRP directs themRNA-ribosome complex to therough ER. There the SRP binds toa receptor site.

Once attached to the ER, the SRP isreleased and the growing polypeptidesnakes through the ER membrane poreinto the cistern.

An enzyme clips off the signal sequence. As protein synthesiscontinues, sugar groups may beadded to the protein.

In this example, the completed proteinis released from the ribosome and foldsinto its 3-D conformation, a process aidedby molecular chaperones.

The protein is enclosed within aprotein coated transport vesicle. Thetransport vesicles make their way tothe Golgi apparatus, where furtherprocessing of the proteins occurs(see Figure 3.19).

Signalrecognitionparticle(SRP) Receptor site

Rough ER cistern

Growingpolypeptide

Signalsequenceremoved

Sugargroup

Releasedprotein

ER signalsequence

Ribosome

CytosolTransport vesiclepinching off

Protein-coatedtransport vesicle

Rough ER cistern

ER signalsequence

Cytosol

Ribosome

Rough ER cistern

ER signalsequence

Cytosol

1 U Once attached to the ER, the SRP isreleased and the growing polypeptidesnakes through the ER membrane poreinto the cistern.

Growingpolypeptide

Ribosome

Rough ER cistern

ER signalsequence

Cytosol

Growingpolypeptide

Sugargroup

Ribosome

Rough ER cistern

ER signalsequence

Cytosol

Growingpolypeptide

Sugargroup

Releasedprotein

Ribosome

Once attached to the ER, the SRP isreleased and the growing polypeptidesnakes through the ER membrane poreinto the cistern.

The protein is enclosed within aprotein coated transport vesicle. Thetransport vesicles make their way tothe Golgi apparatus, where furtherprocessing of the proteins occurs(see Figure 3.19).

Rough ER cistern

Growingpolypeptide

Sugargroup

Releasedprotein

ER signalsequence

Ribosome

CytosolTransport vesiclepinching off

Protein-coatedtransport vesicle

Summary: From DNA to Proteins

• Complementary base pairing directs transfer of genetic information in DNA into amino acid sequence of protein– DNA triplets mRNA codons– Complementary base pairing of mRNA

codons with tRNA anticodons ensures correct amino acid sequence

– Anticodon sequence identical to DNA sequence except uracil substituted for thymine

Figure 3.40 Information transfer from DNA to RNA to polypeptide.

DNA: DNA base sequence(triplets) of the gene codesfor synthesis of aParticular polypeptide chain

DNAmolecule

Gene 1

Gene 2

Codons

Triplets

Anticodon

Stop;detachStart

translation

mRNA: Base sequence(codons) of the transcribed mRNA

tRNA: Consecutive base sequences of tRNAanticodons recognize themRNA codons calling forthe amino acids theytransport

Polypeptide: Amino acidsequence of thepolypeptide chain

Gene 4

1 2 3 4 5 6 7 8 9

Other Roles of DNA

• Intron ("junk") regions of DNA code for other types of RNA:– Antisense RNA

• Prevents protein-coding RNA from being translated

– MicroRNA• Small RNAs that silence mRNAs made by certain

– Riboswitches• Folded RNAs that act as switches regulating

protein synthesis in response to environmental conditions

Cytosolic Protein Degradation

• Autophagy– Cytoplasmic bits and nonfunctional organelles

put into autophagosomes; degraded by lysosomes

• Ubiquitins – Tag damaged or unneeded soluble proteins in

cytosol– Digested by soluble enzymes or proteasomes

Extracellular Materials

• Body fluids-interstitial fluid, blood plasma, and cerebrospinal fluid

• Cellular secretions-intestinal and gastric fluids, saliva, mucus, and serous fluids

• Extracellular matrix–most abundant extracellular material– Jellylike mesh of proteins and

polysaccharides secreted by cells; acts as "glue" to hold cells together

Developmental Aspects of Cells

• All cells of body contain same DNA but cells not identical

• Chemical signals in embryo channel cells into specific developmental pathways by turning some genes on and others off

• Development of specific and distinctive features in cells called cell differentiation

Apoptosis and Modified Rates of Cell Division

• During development more cells than needed produced (e.g., in nervous system)

• Eliminated later by programmed cell death (apoptosis)– Mitochondrial membranes leak chemicals that

activate caspases DNA, cytoskeleton degradation cell death

– Dead cell shrinks and is phagocytized

Apoptosis and Modified Rates of Cell Division

• Organs well formed and functional before birth

• Cell division in adults to replace short-lived cells and repair wounds

• Hyperplasia increases cell numbers when needed

• Atrophy (decreased size) results from loss of stimulation or use

Theories of Cell Aging

• Wear and tear theory-Little chemical insults and free radicals have cumulative effects

• Mitochondrial theory of aging–free radicals in mitochondria diminish energy production

• Immune system disorders-autoimmune responses; progressive weakening of immune response; C-reactive protein of acute inflammation causes cell aging

Theories of Cell Aging

• Most widely accepted theory– Genetic theory-cessation of mitosis and cell

aging programmed into genes• Telomeres (strings of nucleotides protecting ends

of chromosomes) may determine number of times a cell can divide

• Telomerase lengthens telomeres– Found in germ cells; ~ absent in adult cells

© 2013 Pearson Education, Inc. Cell Cycle Defines changes from formation of cell until it...

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