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DNA Replication, Mitosis and the Cell Cycle
Prokaryotic Cell Division
Asexual Reproduction in Prokaryotes
Why do multicellular organisms need their cells to divide?
Body growth
Why do multicellular organisms need their cells to divide?
Replace cells
Why do multicellular organisms need their cells to divide?
Reproduction (MEIOSIS)
Reproduction and Cell Division
• Asexual Reproduction – replicate DNA, split cell contents in half, make genetically identical offspring (except for occasional mutations)– Mitosis ONLY
• Sexual Reproduction – make genetically different offspring from fusion of sex cells– Meiosis – makes sex cells or gametes
– Mitosis – Cell division after fertilization and to replace dead cells after apoptosis
6 weeks pregnant 10 weeks pregnant 20 weeks pregnant 40 weeks pregnant
DNA Replication
• Before any cell can divide, must make a copy of WHOLE genome
• Semiconservative – each new DNA molecule conserves half of the original DNA
• Done using various enzymes (proteins) to attract and bond new nucleotides
DNA Replication
Proteins in DNA replication
Binding proteins stabilize each strand.
Primase creates an RNA primer
Helicase unpackages an organism’s genes
DNA polymerase creates DNA molecules by assembling nucleotides
Ligase facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond
DNA Replication• Helicase separates strands.• Single strand binding proteins
prevent strands from rejoining.• Primase makes a short stretch
of RNA on the DNA template.
DNA Replication• DNA polymerase adds DNA
nucleotides to the RNA primer.
DNA Replication• Discontinuous synthesis
produces Okazaki fragments on the lagging strand
DNA Replication• Enzymes replace RNA primers
with DNA. Ligase seals the sugar–phosphate backbone.
Preparation for Cell Division
• Replicated DNA condenses into CHROMOSOMES
• Chromosome made of chromatin
– DNA, proteins (enzymes that help DNA replicate, transcribe, translate)
– Nucleosome – 1 stretch of DNA + 8 proteins
• Makes a “necklace” of DNA
• 1 Replicated chromosome
– 2 sister chromtids (contains DNA, proteins, etc)
– 1 centromere – attaches sister chromatids together
Chromosomes
Replicated Chromosome
Chromosome Terms
Term Definition
Chromatina complex of macromolecules found in cells, consisting of DNA, protein and RNA
Chromosome
a single piece of coiled double-stranded DNA, containing many genes, regulatory elements and other non-coding DNA
The prokaryotes—bacteria and archaea—typically have a single circular chromosome, but many variations exist. In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin.
Chromatidone copy of a duplicated chromosome, which is generally joined to the other copy by a single centromere
Centromere the part of a chromosome that links sister chromatids
Mitosis
• Cell Cycle – Events that occur from 1 cell division to the next– Occurs 300 million times/minute
• Interphase –– No cell division
– Protein synthesis, DNA replication
• Cytokinesis –– Splitting of the cell (organelles, cytoplasm, and
membranes)
Cell Cycle
Interphase
• G1 – normal cell function
– Nerve cells permanently in G0 (non-dividing phase) –no growth of brain or repair after adulthood
• S Phase – DNA replication, repair damaged DNA
– End of S phase have replicated chromosome with 2 sister chromatids
– In animal cells – centrosomes move chromosomes around for division phase
• G2 – continued growth and prep for division
– Chromosomes wind more tightly, proteins produced
– End of interphase
Division Phase
• Prophase – DNA coils tightly into condensed chromosomes
– Random arrangement in nucleus
– Centrosomes migrate to poles (animals)
– Nucleolus disappears
• Prometaphase– Immediately after formation of mitotic spindle
– Nuclear envelop disappears
– Kinetochores assemble on centromere
Division Phase
• Metaphase –– Mitotic spindle aligns chromosomes on equator of cell
• Anaphase– Mitotic spindle splits chromosome at centromere– Pulls sister chromatids to opposite ends of cell
• Telophase– Reverse of prophase and prometaphase– Mitotic spindle breaks down– Chromosomes unwind
• Nuclear envelope and nucleolus reappear
Division Phase
• Cytokinesis
– Division of organelles, cytoplasm, macromolecules evenly divide in to daughter cells
– Animal Cells – cleavage furrow – indentation at middle of cell, signals beginning of cytokinesis
– Plan Cells – Cell plate begins to form between new cells, signals beginning of cytokinesis
Cell Cycle: Interphase (before Mitosis begins)
Interphase
Cell Cycle: Prophase
Prophase
Cell Cycle: Metaphase
Metaphase
Cell Cycle: Anaphase
Anaphase
Cell Cycle: Telophase
Telophase
Cell Cycle: Cytokinesis
Cell Division TermsTerm Definition
Interphase the phase of the cell cycle in which the cell spends the majority of its time and prepares for cellular division
G0 phase the cell functions normally; occurs in cells that do not divide often (or ever)
G1 phase the cell grows and functions normally
G2 phase the cell resumes its growth in preparation for division
S phase the cell duplicates its DNA
Mitosis the process by which cells replicate
Prophase a stage of mitosis in which the chromatin condenses into chromosomes
Prometaphase the nuclear membrane breaks apart into numerous "membrane vesicles,” and the chromosomes inside form protein structures called kinetochores
Metaphase chromosomes align in the equator of the cell before being separated into the two daughter cells
Anaphase chromosomes are split move to opposite poles of the cell
Telophase the final stage in both meiosis and mitosis
Centrosome an organelle that serves as a regulator of cell-cycle progression
Mitoic spindle the subcellular structure that segregates chromosomes between daughter cells
Kinetochore the protein structure on chromatids where the spindle fibers attach during cell division
Cytokinesis the process in which the single eukaryotic cell is divided to form two daughter cells
Cleavage furrow the indentation of the cell's surface that begins the progression of cleavage, by which some cells undergo cytokinesis
Cell plate the plate that causes cytokinesis in plant cells
Evolution of Sexual Reproduction
• Combining genes from two individuals
• First form of gene exchange – conjugation
– Outgrowth of bacterial cell – Sex pilus to transfer gene material to another bacteria
– Still used today
• Paramecium – uses bridge of cytoplasm to exchange nuclei
Sexual Reproduction and Chromosomes
• Diploid Cell (2n) – 2 full sets of chromosomes– 1 set of chromosomes from each parent– You have 46 chromosomes
• 23 from Mom, 23 from Dad
• Karyotype – size ordered chart of all chromosomes in a cell
• Autosomes – body chromosomes, same for male and female, 22 pairs
• Sex Chromosomes – determine an individual’s sex, different for male and female– Male – XY– Female – XX
Human Karyotype
Chromosomes
• Pairs of chromosomes are HOMOLOGOUS– Matching pair that look alike and have same
sequence of genes
– NOT identical
– Have difference versions of a gene – ALLELES• Can be brown eyes/blue eyes
• Can be codes for melanin/does not code for melanin
• Sex Chromosomes –– NOT homologous – different sizes and number of
genes
Homologous Pair of Chromosomes
Gametes
• Gametes = Sex Cells (egg and sperm)
– Haploid (n) – half the amount of genetic material
• ONLY 1 set of chromosome
• For you – 23
• Fertilization – fusion of 2 HAPLOID gametes to make DIPLOID zygote
– Zygote divides by MITOSIS for make new individual
Meiosis
• Meiosis – process by which gametes are produced
– Makes genetically DIFFERENT gametes
– Occurs in germ cells
– Occurs in testes or ovaries
– Divides the amount of genetic material in HALF
• Start with 46, after meiosis have 23
– Start with 1 cell end up with 4
Mei
osi
s
Meiosis
• DNA replicates once, nucleus divides twice– 2 rounds of cell division – only 1 interphase
• Prophase I– REPLICATED chromosomes condense, spindle forms,
centrosomes, form, nuclear envelop breaks down, HOMOLOGOUS chromosomes line up next to each other
• Metaphase I– Paired homologous chromosomes line up on equator of
cell
• Anaphase I, Telophase I, Cytokinesis– Homologous pairs pull apart (NOT chromatids), separate
into 2 daughter cells and have opposite of prophase
Meiosis
• Meiosis II uses daughter cells from Meiosis I to form 4 haploid gametes
• NO INTERPHASE = NO DNA REPLICATION
• Phases now resemble mitosis– Prophase II – chromosomes condense, spindle and
centrosomes form, nuclear envelop breaks down
– Metaphase II – chromosomes line up on equator
– Anaphase II – Sister chromatids pull apart
– Telophase/Cytokinesis – opposite of prophase and splitting of cells
Meiosis End Game
• 1 diploid germ cell (spermatocyte/oocyte)
• 1 round of DNA replication (Interphase I)
• 2 rounds of cell division
– Meiosis I and Meiosis II
• 4 haploid gametes
– 4 viable sperm
– 1 viable egg and 3 polar bodies
Genetic Variability
• Crossing Over – 2 homologous chromosomes exchange genetic material
– Occurs during prophase I
– Get new combinations of genes on a chromosome
– Result = 4 genetically different sister chromatids
Genetic Variability—Crossing Over
Genetic Variability
• Independent Assortment – chromosomes RANDOMLY align on the equator during meiosis I
– Get different combinations of chromosomes
– Number of possible combinations = 2n
• Where n is the number of homologous pairs
223 = 8,388,608
Genetic Variability Independent Assortment
Different arrangements of chromosomes in diploid cells . . .
. . . allow for unique haploid cells.
Genetic Variability
• Random Fertilization – any of the female’s 8,388,608 possible combinations combine with the male’s 8,388,608 combinations
– That give you approximately 70 trillion genetically different possibilities!
– BUT, can have identical twins….hmmmm……
Mitosis and Meiosis
Mitosis• Done in somatic cells• 1 round of cell division• Chromosomes line up on
equator• Pull apart chromosomes• Makes 2 DIPLOID cells• Used for growth,
development, repair• Asexual reproduction
Meiosis• Done in germ cells• 2 rounds of cell division• Homologous pairs line up
on equator• Pull apart homologous
pairs• Makes 4 HAPLOID cells• Used for formation of
gametes • Sexual reproduction
Errors in Meiosis
• Polyploidy – extra 1 or more sets of chromosomes– Ex. Normal sperm (23) + Oops egg (46) = 69– Normally human polyploids do not survive– 30% flowering plants are polyploids and survive
• Nondisjunction – extra or one missing chromosome– 50% spontaneous miscarriages– Ex. Trisomy 21 – Down Syndrome– Ex. Trisomy 18 – Edwards Syndrome– Ex. Trisomy 13 – Patau Syndrome
Errors in Meiosis
• Extra or Missing Sex Chromosomes
Chromosomes Name of Condition Likelihood Symptoms
XXX Triplo-X about once in every 1,000 female births
Symptoms may include tall stature; small head; vertical skinfolds that may cover the inner corners of the eyes; speech and language learning disabilities, such as dyslexia; or weak muscle tone. Increased risk of motor coordination problems and auditory processing disorders, and scoliosis. Because the vast majority of Triple X females are never diagnosed, it may be very difficult to make generalizations about the effects of this syndrome.
XXY Klinefelter Syndrome exists in 1:500 to 1:1000 male live births
Some degree of language learning or reading impairment may be present, although these deficits can often be overcome through early intervention. There may also be delays in motor development which can be addressed through therapy. As they grow older, they tend to become taller than average. Because these boys do not produce as much testosterone as other boys, they have a less muscular body, less facial and body hair, and broader hips. They may develop breast tissue and also have weaker bones, and a lower energy level than other males. Affected males are often infertile, or may have reduced fertility.
XYY Jacobs Syndrome occurs in 1 in 1,000 male births
Average final height approximately 3" above expected final height. Approximately half of XYY boys identified by a newborn screening program had learning difficulties—a higher proportion than found among siblings and above-average-IQ control groups. However, they often have no outstanding difference from XY boys.
XO Turner Syndrome occurs in 1:2000 to1:5000 females
Symptoms include short stature, broad chest, reproductive sterility, increased weight, small fingers, webbed neck, swelling of hands and feet, nonverbal learning disabilities, ADHD, visual impairments, ear infections or hearing loss, heart (aorta) problems, and characteristic facial features.
Chromosomal Abnormalities
• Chromosomal Deletion – Loss of one or more genes– Ex. Cri du chat - several missing genes at chrom. 5
• Chromosomal Duplication – makes multiple copies of parts of chromosome– Ex. Fragile X – extra CGG sequence (10 – 200)
– Not always harmful
• Inversion – Part of chromosome flips and reinserts at a different location
• Translocation – nonhomologous chromosomes exchange parts– Usually results in leukemia or other cancers
Spermatogenesis
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Secondary spermatocytes
(haploid) Spermatids (haploid) Sperm (haploid)
Maturation
Y
X
X
YY
Primary spermatocyte
(diploid)
Germ cell
Spermatogonium
(diploid)
Haploid (n)
Diploid (2n)
X
Y
Autosomes
Spermatogonium
MEIOSIS II
MEIOSIS II
Sex
chromosomes
X
Y
X
MITOSIS
MEIOSIS I
Spermatogenesis
Oogenesis
Out of Control Cell Division
• Proteins regulate cell cycle– Cyclins – fluctuate depending on cell phase
– Interactions of all cyclins make checkpoints during cycle• Cell will not go past a check point until cyclin
concentrations change
– Checkpoints• G1 – screens for DNA damage, if damaged, cell dies
• S Phase – Lots of checkpoints during DNA replication
• G2 – makes sure 2 full sets of chromosomes
• Metaphase – ensures all chromosomes are aligned correctly
Cell Division Checkpoints
DNA damaged?
DNA replicatingright?
• All DNA replicated?• Damaged DNA reparable?• Spindle making good to go?
After Metaphase• Spindle built?• Chromosomes
attached?• Chromosomes
aligned?
Requirements for Cell Division
Growth factors
Requirements for Cell Division
Growth factors
Cancer
• No balance between cell division and cell death
• Cell gets through checkpoints– Tumor – abnormal mass of tissue formed from
uncontrolled cell division• Benign – slow growing harmless, capsule enclosed
• Malignant – invades surrounding tissue
• Metastasis – Cells from break away from original tumor and travel blood or lymphatic system
– Cancer – class of diseases characterized by malignant cells
Cancer
• How are cells different?– Uncontrolled cell division– Different shape – rounder, more fluid– Some have multiple nuclei– Immortal – internal clock does not work (50ish cell
divisions)• Telomeres – internal clock, ends of chromosomes that
degrade with each cell division• High amount of telomerase
– Growth Factors – divide even if no factors are present– Contact Inhibition – Normal cells stop dividing when
touch each other in 1 cell layer. • Cancer cells just keep dividing
Cancer
• What causes cancer?– Mutations in 2 classes of cancer-related genes
– Oncogenes – Mutated genes that stimulate cell division• Accelerator of cell division
– Tumor Suppressor Genes – normal genes code for proteins that promote apoptosis• Mutating these genes stop cell death and promote
more cell division– BRAC 1 – Breast cancer gene
Cancer
• Stages of Cancer
– Stage I – start to invade surrounding tissue
– Stage II – Spread to tissue around original affected tissue
– Stage III – Spread to organs and lymph nodes near cancer’s origin
– Stage IV – Spread to distant areas throughout the bode
Cancer
• Diagnosis
– X-ray, CAT scans, MRI’s PET scans, ultrasound
– Endoscope to inspect inside of organs
– Biopsy – cell sample
– Microscopy to id cells from biopsy
– Blood tests – white cell count, tumor markers, proteins
Cancer
• Treatment
– Surgical removal of tumor
– Chemotherapy – intravenous medicine to stop cell division
– Radiation Therapy – directed streams of radioactive isotopes to kill tumor cells
Cancer Cells
Causes: hereditary & environmental
Cancer Cells
Treatment: Taxol
Cancer Cells
Treatment: Taxol
• Created from the Pacific Yew tree.
