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Biology 102Biology 102

Lecture 8: Cell Division and Lecture 8: Cell Division and Cancer Cancer

•• DNA stores all genetic information in the cellDNA stores all genetic information in the cell

•• Codes for all proteinsCodes for all proteins

•• Proteins are the major structural and Proteins are the major structural and

functional component of most organismsfunctional component of most organisms

•• Codes directions for how proteins will be usedCodes directions for how proteins will be used

•• Relies entirely on the sequence of nucleotide Relies entirely on the sequence of nucleotide

basesbases

•• Permanent changes in this sequence are called Permanent changes in this sequence are called mutationsmutations

DNADNA

•• Most DNA mutations alter the protein productMost DNA mutations alter the protein product

•• May…May…

•• Make it function better (rarely)Make it function better (rarely)

•• Change its functionChange its function

•• Reduce its functionReduce its function

•• Make it nonMake it non--functionalfunctional

MutationsMutations

•• Example: CancerExample: Cancer

•• Mutations in portions of DNA that code for Mutations in portions of DNA that code for

proteins that regulate cell growth and divisionproteins that regulate cell growth and division

•• Leads to unregulated cell growthLeads to unregulated cell growth

MutationsMutations

•• To understand cancer, we need to understand To understand cancer, we need to understand

normal cell life cyclenormal cell life cycle

•• Begins and ends with division eventsBegins and ends with division events

•• MitosisMitosis = process of division for most cells= process of division for most cells

•• InterphaseInterphase = time between division events= time between division events

Cell CycleCell Cycle

•• Why do cells divide?Why do cells divide?

•• GrowthGrowth –– allows a single fertilized egg to allows a single fertilized egg to

become a relatively large become a relatively large multicellularmulticellular

organismorganism

•• Adults have more cells than babies!Adults have more cells than babies!

Cell CycleCell Cycle

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•• Why do cells divide?Why do cells divide?

•• ReplacementReplacement–– cells, like those of the skin, cells, like those of the skin,

wear out at a predictable pacewear out at a predictable pace

•• Example: Small intestineExample: Small intestine

Cell CycleCell Cycle

•• Why do cells divide?Why do cells divide?

•• ReproductionReproduction–– most most multicellularmulticellular organisms organisms

produce egg and sperm cells that permit them produce egg and sperm cells that permit them

to produce offspringto produce offspring

•• Meiosis Meiosis –– more on that later!more on that later!

Cell CycleCell Cycle

•• Why do cells divide?Why do cells divide?

•• RepairRepair –– accidents happen!accidents happen!

Cell CycleCell Cycle

•• InterphaseInterphase is the phase between cell divisionsis the phase between cell divisions

•• Cell spends most of its time hereCell spends most of its time here

•• Cell performs its functions hereCell performs its functions here

•• DNA present as DNA present as chromatinchromatin

Cell CycleCell Cycle

•• InterphaseInterphase has 3 stages as the cell prepares for has 3 stages as the cell prepares for

divisiondivision

1. 1. GG11 phasephase –– 88--12 hours (or longer)12 hours (or longer)

•• “Growth 1” or “Gap 1” Phase“Growth 1” or “Gap 1” Phase

•• Cell manufactures Cell manufactures cytoskeletalcytoskeletal elements elements

and organelles for 2 cellsand organelles for 2 cells

•• Mitochondria divideMitochondria divide

InterphaseInterphase

•• Exiting the cell cycleExiting the cell cycle

•• After G1, some cells enter a quiescent stateAfter G1, some cells enter a quiescent state

•• Some reSome re--emerge after a timeemerge after a time

•• Some remain quiescent for the life of the Some remain quiescent for the life of the

organism (muscle cells, neurons)organism (muscle cells, neurons)

GG00 PhasePhase

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•• InterphaseInterphase has 3 stages as the cell prepares for has 3 stages as the cell prepares for

divisiondivision

2. 2. S phaseS phase –– 66--8 hours8 hours

•• “Synthesis” phase“Synthesis” phase

•• DNA is replicatedDNA is replicated

InterphaseInterphase

•• InterphaseInterphase has 3 stages as the cell prepares for has 3 stages as the cell prepares for

divisiondivision

3. 3. GG22 phasephase –– 22--5 hours5 hours

•• “Growth 2” phase“Growth 2” phase

•• Period of rapid cell growth and lastPeriod of rapid cell growth and last--minute minute

protein synthesisprotein synthesis

•• Cell is preparing to divideCell is preparing to divide

•• Some cells skip this stageSome cells skip this stage

•• Frog embryos, cancerFrog embryos, cancer

InterphaseInterphase

•• InterphaseInterphase ends when cells begin M phaseends when cells begin M phase

•• “Mitosis” and “Mitosis” and cytokinesiscytokinesis

•• Duplication and division of nucleus and the Duplication and division of nucleus and the

entire cellentire cell

•• Has its own steps (which we will cover in lab)Has its own steps (which we will cover in lab)

M PhaseM Phase

•• Exist to make sure a cell is healthy, normalExist to make sure a cell is healthy, normal

•• Don’t want to replicate mutated DNA!Don’t want to replicate mutated DNA!

•• Three major checkpointsThree major checkpoints

•• GG11/S/S –– check for sufficient growth, damaged check for sufficient growth, damaged

DNA, sufficient preparationsDNA, sufficient preparations

•• GG22/M/M –– check for DNA damage in replicated check for DNA damage in replicated

chromosomes, is everything ready?chromosomes, is everything ready?

•• MM –– check for proper spindle formation just check for proper spindle formation just

before cell dividesbefore cell divides

Cell Cycle CheckpointsCell Cycle Checkpoints

•• Depend on proteins involved in cell cycle Depend on proteins involved in cell cycle

regulationregulation

•• Best understood is a tumor suppressor called Best understood is a tumor suppressor called

p53p53

Cell Cycle CheckpointsCell Cycle Checkpoints

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•• Normal cell:Normal cell:

DNA p53 Cell cycle RepairDNA p53 Cell cycle Repair

Damaged Produced ArrestDamaged Produced Arrest

•• Cancer cell:Cancer cell:

DNA No p53 UncontrolledDNA No p53 Uncontrolled

Damaged Produced Cell growthDamaged Produced Cell growth

p53 and Cancerp53 and Cancer

•• p53 is frequently mutated in cancerp53 is frequently mutated in cancer

•• Cancer can occur in any tissueCancer can occur in any tissue

•• Most common (National Cancer Institute)Most common (National Cancer Institute)

1.1. ProstateProstate

2.2. BreastBreast

3.3. LungLung

4.4. ColorectalColorectal

p53 and Cancerp53 and Cancer

•• Cancer treatments target rapidly dividing cellsCancer treatments target rapidly dividing cells

•• Problem: some normal cells divide rapidlyProblem: some normal cells divide rapidly

•• Small intestineSmall intestine

•• Cells for hair growthCells for hair growth

•• Bone marrowBone marrow

•• Leads to common side effects of cancer Leads to common side effects of cancer treatmentstreatments

•• Weight lossWeight loss

•• Hair lossHair loss

•• AnemiaAnemia

CancerCancer

•• Primary type of cell divisionPrimary type of cell division

•• Used by all cells except sperm and eggsUsed by all cells except sperm and eggs

•• Produces two genetically identical daughter cellsProduces two genetically identical daughter cells

•• Replication must occur prior to mitosisReplication must occur prior to mitosis

MitosisMitosis

Replication fork

•• Creates two identical DNA molecules, each called Creates two identical DNA molecules, each called

a a chromatidchromatid

•• The two identical molecules are called The two identical molecules are called sister sister chromatidschromatids

•• Sister Sister chomatidschomatids separate during mitosis, with separate during mitosis, with one going into each daughter cellone going into each daughter cell

Replication (S phase)Replication (S phase)

•• Sister Sister chromatidschromatids become attached to each become attached to each

other at the other at the centromerecentromere

•• Condense to become Condense to become chromosomeschromosomes

ChromosomesChromosomes

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•• Chromosomes are large enough to be seen by Chromosomes are large enough to be seen by

light microscopelight microscope

•• Chromosomes are only present when a cell is Chromosomes are only present when a cell is preparing to dividepreparing to divide

ChromosomesChromosomes

•• Takes place in several stagesTakes place in several stages

•• We We will explore these stages in detail in labwill explore these stages in detail in lab

MitosisMitosis MitosisMitosis

•• Important for now:Important for now:

•• Used by every cell except sperm and eggsUsed by every cell except sperm and eggs

•• Creates two genetically identical daughter Creates two genetically identical daughter

cellscells

•• Identical to each other AND to the parent Identical to each other AND to the parent

cellcell

•• DNA must be replicated before mitosis can DNA must be replicated before mitosis can beginbegin

MitosisMitosis

•• Very important to see what happens to the Very important to see what happens to the

number of chromosomes at each phase of the number of chromosomes at each phase of the cell cycle:cell cycle:

MitosisMitosis

Phase of the Cell Cycle Human Cell Chromosome Number Significant Event(s)

G1 (and G0) 46 Duplicate organelles

S 92 DNA replication

Mitosis 92 Sister chromosomes separate

Cytokinesis 46 Daughter cells produced

M phaseM phase

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•• Remember the goals of cell division…Remember the goals of cell division…

•• GrowthGrowth

•• ReplacementReplacement

•• ReproductionReproduction

•• RepairRepair

•• For some species, mitosis is sufficient for all 4For some species, mitosis is sufficient for all 4

•• Not the case for species that use sexual Not the case for species that use sexual reproductionreproduction

Cell DivisionCell Division

•• Offspring genetically identical to parentOffspring genetically identical to parent

•• All use variants of mitosisAll use variants of mitosis

•• Some advantages…Some advantages…

•• Major disadvantage: no opportunity to recombine Major disadvantage: no opportunity to recombine genetic materialgenetic material

Asexual ReproductionAsexual Reproduction

Organism Benefit(s) of Asexual Reproduction

Bacteria

Strawberry plant

Sea anemone

(also yeast)

Examples of Asexual Reproduction

Binary fission - rapid reproduction if

conditions are right

Spread via runners (no pollination needed) -

rapid reproduction

Budding (don't wait for a mate) - rapid

reproduction

•• Two individuals combine genetic materialTwo individuals combine genetic material

•• Gametes fuse to produce offspringGametes fuse to produce offspring

•• In animals…In animals…

•• Male gamete = spermatozoon or spermMale gamete = spermatozoon or sperm

•• Female gamete = ovum or eggFemale gamete = ovum or egg

•• Mitosis will not work to produce the gametesMitosis will not work to produce the gametes

•• Let’s see why…Let’s see why…

Sexual ReproductionSexual Reproduction

•• Generation 1: Parents each have 46 chromosomesGeneration 1: Parents each have 46 chromosomes

Sexual ReproductionSexual Reproduction

46

Ovum

46

Sperm

92

Offspring

•• Generation 2: Parents each have 92 chromosomesGeneration 2: Parents each have 92 chromosomes

Sexual ReproductionSexual Reproduction

92

Ovum

92

Sperm

184

Offspring

•• Generation 3: Parents each have 184 chromosomesGeneration 3: Parents each have 184 chromosomes

Sexual ReproductionSexual Reproduction

184

Ovum

184

Sperm

368

Offspring

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•• Solution: produce gametes with half the number Solution: produce gametes with half the number

of chromosomes = of chromosomes = meiosismeiosis

•• Human somatic cells = 46 chromosomesHuman somatic cells = 46 chromosomes

•• 2 copies of each (diploid, 2N)2 copies of each (diploid, 2N)

•• Human gametes = 23 chromosomesHuman gametes = 23 chromosomes

•• 1 copy of each (haploid, N)1 copy of each (haploid, N)

MeiosisMeiosis

23

Ovum

23

Sperm

46

Offspring

•• Can’t simply take 46 chromosomes and randomly Can’t simply take 46 chromosomes and randomly

put 23 in each daughter cellput 23 in each daughter cell

•• Each chromosome must have a copy in each Each chromosome must have a copy in each

daughter celldaughter cell

•• Somatic cells are diploidSomatic cells are diploid

•• Two copies of each chromosomeTwo copies of each chromosome

•• Two versions of same chromosome are said to Two versions of same chromosome are said to be be homologoushomologous

•• Homologous chromosomes are separated when Homologous chromosomes are separated when

cells dividecells divide

MeiosisMeiosis

•• Again, we will examine this in much more detail in Again, we will examine this in much more detail in

lablab

•• Important for now:Important for now:

•• Begins with DNA replicationBegins with DNA replication

•• Same stages as mitosis, but each occurs twiceSame stages as mitosis, but each occurs twice

•• Results in 4 haploid daughter cellsResults in 4 haploid daughter cells

MeiosisMeiosis

•• In humans used exclusively to produce gametesIn humans used exclusively to produce gametes

•• Called Called gametogenesisgametogenesis

•• Process is almost the same…Process is almost the same…

MeiosisMeiosis

SpermatogenesisSpermatogenesis

1.1. Starts at pubertyStarts at puberty

2.2. Produces 4 viable sperm Produces 4 viable sperm cellscells

3.3. Potentially unlimitedPotentially unlimited

OogenesisOogenesis

1.1. Starts before birth Starts before birth (~400,000!!)(~400,000!!)

2.2. Continues at puberty but Continues at puberty but arrests at M2arrests at M2

3.3. Completed only if Completed only if fertilizedfertilized

4.4. Produces 1 viable egg and Produces 1 viable egg and 3 polar bodies3 polar bodies

5.5. Stops at menopauseStops at menopause

MeiosisMeiosisSpermatogenesisSpermatogenesis OogenesisOogenesis

46

92

46 46

46

92

46

2323 23 23 23

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•• Chromosomes do not properly separate into Chromosomes do not properly separate into

daughter cellsdaughter cells

•• Can happen in mitosis; much more likely in Can happen in mitosis; much more likely in

meiosismeiosis

Chromosome NonChromosome Non--DisjunctionDisjunction

•• Abnormal gamete can participate in fertilization Abnormal gamete can participate in fertilization

with a normal gametewith a normal gamete

•• Offspring either…Offspring either…

•• Have one copy of a chromosome Have one copy of a chromosome

•• MonosomyMonosomy

•• Nearly always fatalNearly always fatal

•• Exception: Turner Syndrome (XO)Exception: Turner Syndrome (XO)

•• Have 3 copies of a chromosome Have 3 copies of a chromosome

•• TrisomyTrisomy

•• Usually fatal, some exceptionsUsually fatal, some exceptions

Chromosome NonChromosome Non--DisjunctionDisjunction

•• TrisomyTrisomy 13 13 –– PatauPatau SyndromeSyndrome

•• 80% fatal in first year80% fatal in first year

•• TrisomyTrisomy 18 18 –– Edward’s SyndromeEdward’s Syndrome

•• 50% fatal in first year50% fatal in first year

•• TrisomyTrisomy 21 21 –– Down SyndromeDown Syndrome

•• Survival to adulthood commonSurvival to adulthood common

TrisomyTrisomy

•• Also occurs in sex chromosomesAlso occurs in sex chromosomes

•• TrisomyTrisomy X (XXX) X (XXX)

•• KlinefelterKlinefelter Syndrome (XXY) Syndrome (XXY)

•• Jacob Syndrome (XYY) Jacob Syndrome (XYY)

•• YYY doesn’t exist, but YYO is fatalYYY doesn’t exist, but YYO is fatal

•• More on these laterMore on these later

TrisomyTrisomy Is This Is This KaryotypeKaryotype Normal?Normal?