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http://www.nobelprize.org/educational/medicine/2001/index.html
http://www.cellsalive.com/mitosis.htm
KEY ROLES OF CELL DIVISION
ReproductionGrowthRepairDistribution of genetic material
• Genome, somatic cells, gametes
• Chromatin, chromosomes, sister chromatids, centromere
Genetic Material
• Chromatin
• Chromosomes
• Chromatids
• Centromere
GrowthMetabolic activity Chromosomes
replicate
Centrioles replicateProtein syn. microtubules
CELL CYCLE
colchicine
Single, circular chromosomeNo mitosisOrigin of replicationCell wall extends between
mesosomes
Cell Cycle Controls• G0 (nondividing)
• G1 (restriction point)
• G2
• M
Cell Cycle Controls
• Cyclin: cyclic conc. fluctuations; accum. G1 & S
• Cdks: concentration stable, activity changes
• MPF: maturation promoting factor, acts at the G2 checkpoint triggering mitosis by phosphorylating proteins; breaks down its cyclin
INTERNAL & EXTERNAL CUES
• Kinetochore messages: anaphase promoting complex (APC) inactive until all kinetochores are attached to spindle.
• Growth factors: proteins that stimulate cell division.– Platelet derived growth factor– Density dependent inhibition– Anchorage dependence
Cancer: tumor, benign tumor, malignant tumor, metastasis
http://www.hhmi.org/biointeractive/dna/DNAi_replication_vo2.html
http://www.wiley.com/college/pratt/0471393878/student/animations/dna_replication/index.html
http://www.johnkyrk.com/DNAreplication.html
DNA ERWIN CHARGAFF: analyzed nuclei of many species
– Base pairing rules (1:1 ratios)– Concentration of cytosine & guanine equal– Concentration of adenine & thymine equal
ROSALIND FRANKLIN & MAURICE WILKINS‒ X-ray diffraction
WATSON & CRICK‒ DNA Model‒ Proposed semi conservative replication
• Double helix• Double strand of
nucleotides (deoxyribose, phosphate, nitrogen base) held together by H-bonds
• Anti-parallel strands• Purines: adenine &
guanine (double rings)• Pyrimidines: thymine &
cytosine (single rings)
DNA STRUCTURE
NOTE: # of H-bonds between bases, measurements, anti-parallel strands
DNA REPLICATION
DNA REPLICATION
DNA REPLICATION
DNA REPLICATION
http://highered.mcgraw-hill.com/sites/0072943696/student_view0/chapter3/animation__dna_replication__quiz_1_.html
DNA REPLICATION
Given one strand of DNA, what is the base sequence of the complimentary strand?
ACGTTGCAAGCTGACCTGGTCAG
REPLICATION MODELS
MESELSON & STAHL PROVE SEMICONSERVATIVE
REPLICATION
MESELSON & STAHL PROVE SEMICONSERVATIVE
REPLICATION
DNA has two “heavy” strands
DNA is now hybrid; ½ heavy, ½ light
MESELSON & STAHL PROVE SEMICONSERVATIVE REPLICATION
Conservative replication proven wrong.
Semi-conservative & dispersive still possible (all strands hybrids)
MESELSON & STAHL PROVE SEMICONSERVATIVE REPLICATION
After another replication (on “light” medium), semi-conservative replication confirmed (1/2 hybrid & ½ light)
Predict the next generation!
DNA replication:- DNA polymerases catalyze the reaction- Hydrolysis of phosphate bonds provides energy
DNA: anti-parallel strands
• Carbons of deoxyribose numbered 1' - 5'
• Phosphodiester bonds involve the 3' & 5' carbons
• One strand runs 5' to 3'• The other strand runs 3'
to 5'
1. DNA polymerase elongates DNA strands only in the 5' to 3'direction
2. One new strand, the leading strand, can elongate continuously 5' to 3'as the replication fork continues.
3. The other new strand, lagging strand, grows discontinuously in an overall 3' to 5' direction by adding short Okazaki fragments that are built in a 5' to 3' direction.
4. Ligase connects the Okazakifragments.
Priming DNA Synthesis
• Polymerase cannot initiate synthesis, it can only add to the end of an already started strand.
• Primase builds RNA nucleotides into a primer.
• RNA primer eventually replaced by DNA nucleotides
(topoisomerase)
Summary of DNA Replication
Ligasejoins Okazakifragments
Lagging strand-discontinuous synthesis –Okazaki fragments
Helicase unwindsparental double helix
Topoisomerase stabilizes unwound DNA
Leading strand, continuous synthesis
• DNA REPLICATION & MAINTENANCE• DNA Polymerase: enzyme which synthesizes single
DNA strand from template DNA (replication)• Whole nucleotides are bonded to complementary
nucleotides to form each new strand.– Trinucleotides are raw materials (ATP, GTP, TTP, CTP)– 2 (high energy bonds) used to accomplish bonding
(energy expensive); AMP, GMP,TMP,CMP bonded to each other by DNA polymerase.
• Other enzymes involved in maintaining DNA structure.– Recognition enzymes (proof reading enzymes) scan DNA
molecule to identify atypical or injured DNA– Endonucleases (restriction enzymes) – breaks DNA above
& below “atypical” sites.– DNA polymerase – synthesizes single strand segments to
replace “damaged” segments.– DNA ligase – binds new segment to old strand.
ENZYMES WHICH MAINTAIN DNA
•“Scanner” or proofreading enzyme checks DNA for damage
•Endonuclease (restriction enzyme)cuts DNA
•DNA Polymerase adds new nucleotides
•DNA Ligasejoins new nucleotides (S-P)links Okazaki fragments
The end-replication problem:
Gap left at the 5’ end of each chromosome.Each end gets shorter with every replication
Telomeres-short nucleotide sequences at the end of each chromosome.- protect the genes- telomerase, present in germ cells, produces telomeres
Humans: TTAGGG
MEIOSIS
Introduction to Heredity• Offspring inherit chromosomes• Asexual reproduction
• One parent• Offspring identical to parent
• Sexual reproduction• Greater variation• Two parents• Unique gene combinations
Karyotyping
HUMAN LIFE CYCLE
• Somatic cells• Homologous
chromosomes• Sex chromosomes• Autosomes• Gametes• Haploid/diploid• Fertilization (syngamy)• Zygote
• Chromosomes replicate once• Cell divides twice• Homologous (paired, carry different versions of the same genes) chromosomes separate
GENETIC VARIATION
• INDEPENDENT ASSORTMENT – between homologous chromosomes in Meiosis 1 and nonidentical sister chromatids in Meiosis 2 (n=23 8 million possibilities)
• CROSSING OVER – between homologous chromosomes during prophase 1
• RANDOM FERTILIZATION – between ova and sperm (223 x 223 = over 70 trillion)
Independent assortment
Crossing
over