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The Cell Cycle and Cellular ReproductionChapter 9
OutlineDNA and Chromosomes
Cell Division in Prokaryotes
Cell Division in Eukaryotes
The Cell Cycle
Interphase
Mitosis
Cytokinesis
Cell Cycle Control
Apoptosis
The Cell Cycle and Cancer
Characteristics of Cancer
Causes of Cancer
DNA and Chromosomes
DNA serves as information storage molecules.
DNA is made up of nucleotides
Each nucleotide has a sugar, a phosphate group and a nitrogenous (nitrogen-containing) base
The bases are of two main types
Purines – Large bases
Adenine (A) and Guanine (G)
Pyrimidines – Small bases
Cytosine (C) and Thymine (T)
The four nucleotide subunits that make up DNA.
5-C sugar
Nitrogenous base
DNA Double Helix
The two possible
basepairs
Chromosomes
Chromosomes are composed of DNA (40%) and protein (~ 60%).
Chromatin-tangled mass of threadlike DNA and protein in nondividing cell (seen primarily during interphase).
Chromosomes-condensed rod-shaped DNA and protein molecules during cell division.
Chromosomes
A typical human chromosome contains about 140 million nucleotides in its DNA.
In the cell, the DNA is coiled.
The DNA helix is wrapped around positively-charged proteins, called histones.
Eukaryotic chromosomes are linear.
Prokaryotic chromosomes are circular.
Cell CycleSet of events that occur between one cell division and the next.
In prokaryotes and unicellular eukaryotes, cell division is a form of asexual reproduction.
In multicellular eukaryotes, cell division is important for growth, development, and repair.
Plants retain the ability to divide throughout their life span
In mammals, cell division is necessary:
Fertilized egg becomes an embryo
Embryo becomes a fetus
Allows a cut to heal or a broken bone to mend
9
Function of Mitosis
Permits growth and repair.In plants it retains the ability to divide throughout the life of the plant
In mammals, mitosis is necessary:Fertilized egg becomes an embryo
Embryo becomes a fetus
Allows a cut to heal or a broken bone to mend
Functions of Cell Division
Prokaryotes Have a Simple Cell Cycle
The DNA of prokaryotes is a single circular chromosome.
Cell division in prokaryotes takes place in two stages.
The DNA is replicated.
The cell elongates, then splits into two identical daughter cells.
The process is called binary fission (asexual reproduction).
Binary Fission of Prokaryotes
Cell division in eukaryotes is more complex than in prokaryotes because
1. Eukaryotic DNA is packaged differently.
It is in linear chromosomes compacted with proteins.
2. Eukaryotes contain far more DNA.
Levels of Eukaryotic Chromosome Organization
Chromosome Number in Eukaryotes
The number of chromosomes varies from species to species.
Diploids have two chromosomes of each type.Humans have 23 different types of chromosomes
Each type is represented twice in each body (somatic) cell- diploid.Only sperm and eggs have one of each type- haploid.
The n number for humans is n=23Two representatives of each typeMakes a total of 2n=46 in each nucleus of a body cell.
One set of 23 from individual’s father (paternal).Other set of 23 from individual’s mother (maternal).
Chromosome Numbers of Some Eukaryotes
Chromosomes
Humans have 46 chromosomes.
This display is termed a karyotype.
The 23 pairs of chromosomes can be organized by size.
Eukaryotic Cell Cycle
The major stages of the eukaryotic cell cycle:
Interphase
Mitosis
Cytokinesis
Interphase and mitosis each have several substages.
The Cell Cycle
InterphaseLongest phase of the cell cycle.
Normal cell functions occur as well as preparation for cell division.
G1 phase:
Cell doubles its organellesAccumulates materials needed for DNA synthesis
S phase:DNA replication (synthesis)Chromosomes enter with 1 chromatid eachChromosomes leave with 2 identical chromatids each
G2 phase:
Between DNA replication and onset of mitosis (or meiosis)Cell synthesizes proteins necessary for division
Such as microtubules for the mitotic spindle
Mitosis (M) Stage Also called karyokinesis
Nuclear division
Occurs in somatic (non-reproductive) cells in animals
Occurs in meristematic tissues in plants
Daughter chromosomes divided between two daughter nuclei
Four Phases (PMAT)
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis (C) Stage
Cytoplasmic division
Results in two genetically identical diploid daughter cells.
In animal, structure that forms to separate two cells is called a cleavage furrow.
In plant cells, structure that forms to separate two cells is called a cell plate.
At end of S phase of interphase: Each chromosome is duplicated. Consists of two identical DNA double helix chains
Called sister chromatids Attached together at a single point called a centromere
During mitosis: Centromeres holding sister chromatids together split Sister chromatids separate Each becomes a daughter chromosome Sisters of each type distributed to opposite daughter nuclei
Duplicated Chromosome
Mitosis in Animal Cells
Outside nucleus is the centrosome The centrosome was replicated in S-phase.
Now two centrosomes This is the microtubule organizing center. Organizes the mitotic spindle Each composed of a bundle of microtubules In animals, contains two barrel-shaped centrioles.
Oriented at right angles to each other within centrosome
Prophase
Nuclear envelope breaks down
Nucleolus disappears
Chromatin condenses
Chromosomes distinguishable with microscope
Visible double (two sister chromatids attached at centromere)
Spindle apparatus forms
Two centrosomes move away from each other
Form microtubules in star-like arrays called asters
Prometaphase
Centromere of each chromosome develops two kinetochores
On opposite sides of the centromeres
One over each sister chromatid
Spindle fibers attach at the kinetochores
Physically hook sister chromatids up with spindle apparatus.
Connect sister chromatids to opposite poles of mother cell.
Metaphase Chromosomes align along the equatorial plane of cell
Metaphase plate
Represents plane through which mother cell will be divided
Chromosomes are pulled around by kinetochore fibers
Anaphase Centromere splits
Sister chromatids separate
Now called daughter chromosomes
Pulled to opposite poles by shortening of the microtubules attached to them
Cytokinesis begins in anaphase.
Telophase
Spindle apparatus disappears
Now two clusters of daughter chromosomes
Still two of each type with all types represented
Nuclear envelopes form around the two separate cluster of daughter chromosomes
Chromosomes uncoil and become chromatin again
Nucleolus reappears in each daughter nucleus
Mitosis in Animal Cells
Overview of Mitosis
Nuclear division in which chromosome number stays constant.
DNA replication produces duplicated chromosomes.
Each duplicated chromosome is composed of 2 sister chromatids held together by a centromere.
Sister chromatids are genetically identical.
During mitosis, the centromere divides and each chromatid becomes a daughter chromosome.
Mitotic Phases Summarized
Prophase-nuclear membrane disappears, centrosomes migrate, spindle fibers appear
Prometaphase- the kinetochore of each chromatid is attached to a spindle fiber.
Metaphase-chromosomes line up at equator, associated with spindle fibers
Anaphase-centromeres divide, sister chromatids migrate to opposite poles, cytokinesis begins
Telophase-nuclear membranes form, spindle disappears, cytokinesis occurs
Cytokinesis: Animal Cells
Division of cytoplasm
Divides mother cell’s cytoplasm equally to daughter nuclei
Encloses each in it’s own plasma membrane
Often begins in anaphase
Animal cytokinesis:
A cleavage furrow appears between daughter nuclei
Formed by a contractile ring of actin filaments
Eventually pinches mother cell in two
Cytokinesis in Animal Cells
Cytokinesis: Plant Cells
Rigid cell walls outside plasma membrane do not permit furrowing
Forms a cell plate
Many small membrane-bounded vesicles
Eventually fuse into one thin vesicle extending across the mother cell
The membranes of the cell plate become the plasma membrane between the daughter cells
Cytokinesis in Plant Cells
Special Characteristics of Mitosis in Plants
Same phases as animal cells
Plant cells do not have centrioles or asters
Cytokinesis via cell plate
Mitosis in Plant Cells
Cell Cycle Control
Cell cycle controlled by internal and external signals
External signalsGrowth factors
Received at the plasma membrane
Cause completion of cell cycle
Internal signalsFamily of proteins called cyclins
Must be present for stages to progress.
Increase and decrease as cell cycle continues
Without them cycle stops at G1, M or G2
Allows time for any damage to be repaired
The Cell Cycle
Some cells do not go through the cell cycle. These cells are in the G0 stage-extended rest period; cell are still metabolically active; for example, some muscle cells and neurons.
G1 checkpoint
Cell growth is assessed at G1 checkpointProtein p53 stops cycle if DNA damaged
G2 checkpoint
DNA replication is assessed at G2 checkpointStops cycle if DNA is not done replicating or is damaged
M checkpointSpindle assembly checkpointStops if chromosomes not aligned properly
Cell Increase and Decrease Increase and decrease of cell numbers
Cell division increases number of somatic cellsMitosis-division of nucleus of cellCytokinesis-division of cytoplasmOccurs throughout life; important for growth, development, and repair in multicellular organisms
Apoptosis- programmed cell death decreases cell number
Occurs throughout life alsoPrevents abnormal cells from proliferatingSignal protein P53
Stops cycle at G1 when DNA damagedInitiates DNA attempt at repairIf successful, cycle continues to mitosisIf not, apoptosis is initiated
ApoptosisProgressive series of events resulting in cell destruction.
Cells rounds up, and lose contact with surrounding cells.
Nucleus breaks up and DNA undergoes fragmentation.
Mediated by enzymes called caspases.
Apoptosis
During fetal development, many cells are programmed to die
Human cells appear to be programmed to undergo only so many cell divisions
About 50 in cell cultures
Only cancer cells can divide endlessly Programmed cell death
Fingers and toes form from these paddlelike
hands and feet
Cancer is unrestrained cell growth and division
The result is a cluster of cells termed a tumor.
Benign tumors
Encapsulated and noninvasive
Malignant tumors
Not encapsulated and invasive
Leave the tumor and spread throughout the body
Invade other tissues and form new tumors
Can undergo metastasis
The Cell Cycle and Cancer
48
Progression of Cancer
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primary tumor
New mutations arise, and one cell (brown) has the ability to start a tumor.
Cancer in situ. The tumor is at its place of origin. One cell (purple)mutates further.
Cancer cells now have the ability to invade lymphatic and blood vesselsand travel throughout the body.
New metastatic tumors are found some distance from the primary tumor.
lymphaticvessel
bloodvessel
lymphaticvessel
bloodvessel
Characteristics of Cancer Cells
Lack differentiation
Have abnormal nuclei
Form tumors
Mitosis controlled by contact with neighboring cells – contact inhibition
Cancer cells have lost contact inhibition
Undergo metastasis
Original tumor easily fragments
New tumors appear in other organs
Undergo angiogenesis
Formation of new blood vessels
Carcinogenesis – development of cancer
Causes of Cancer Most cancers result from mutations in growth-regulating genes.
There are two general classes of these genes.1. Proto-oncogenes
Encode proteins that stimulate cell divisionIf mutated, they become oncogenes.
2. Tumor-suppressor genesEncode proteins that inhibit cell division
Retinoblastoma (Rb) protein acts during G1 checkpoint to inhibit cell divisionp53 protein
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Cytoplasm
Rasprotein
Srckinase
Rbprotein p53
protein
Cell cyclecheckpoints
Mammalian cell
Proto-oncogenes
Tumor-suppressor Genes
Growth factor receptor:more per cell in manybreast cancers.
Ras protein:activated by mutationsin 20–30% of all cancers.
Rb protein:mutation in 40% of all cancers.
p53 protein:mutated in 50% of all cancers.
(a) In a normal cell there are few Her2 membrane receptors so cell division is controlled.
(b) Some cancer cells have excess Her2 receptors. These cells divide at an increased rate when growth factors are present.
Her2 membrane receptor
Her2 gene on DNA
Growth factor
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Growth Factor Receptor Her2
and Cancer
Herceptin: Breast Cancer Treatment
Retinoblastoma Protein
p53 and Control of the Cell Cycle
The p53 gene plays a key role in the G1 checkpoint of cell division
p53 is also called the guardian angel gene of the cell
The p53 protein (the gene’s product), monitors the integrity of DNA
If DNA is damaged, the protein halts cell division and stimulates repair enzymes.
If the p53 gene is mutatedCancerous cells repeatedly divide even if the DNA is damaged.No stopping at the G1 checkpoint.
Telomerase
Chromosomes have caps on their ends called telomeres.Every time the cell divides part of the cap breaks off.Eventually the cap becomes so small that the chromosome cannot be copied; limits the life span of the cell (~50 cell divisions).Telomerase is the enzyme that can repair the ends of chromosomes.In normal cells telomerase is inhibited so the cell will eventually stop dividing.In cancer cells telomerase is not inhibited, so the telomeres don’t shorten; no limit on the life span of the cell.
Causes of CancerChemicalsRadiationVirusesMutations in specific genes on chromosomes; for example a mutant p53 geneChromosomal mutations- extra chromosomes or missing parts of chromosomesTelomerase
