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