The MOLECULAR Basis of Inheritance.

Structure &

Function!!!

Searching for Genetic Material, I Mendel: modes of heredity in pea plants Morgan: genes located on chromosomes Griffith: bacterial work; transformation: change in genotype

and phenotype due to assimilation of external substance (DNA) by a cell

Avery: transformation agent was DNA

Searching for Genetic Material, II

Hershey and Chase used bacteriophages (phages) to deduce that:

– √ DNA (not protein) is the hereditary material Experiment: sulfur(S) is in protein, phosphorus (P) in DNA;

only P was found in host cell

DNA Structure

Chargaffratio of nucleotide bases (A=T; C=G)

Watson & Crick (Wilkins, Franklin)

The Double Helix √ nucleotides: nitrogenous base (thymine, adenine, cytosine, guanine); sugar deoxyribose; phosphate group

DNA Bonding

Purines: ‘A’ & ‘G’ Pyrimidines: ‘C’ & ‘T’

(Chargaff rules) ‘A’ H+ bonds (2) with ‘T’ ‘C’ H+ bonds (3) with ‘G’ Van der Waals

attractions between the stacked pairs

DNA Structure

Campbell Animation

DNA Replication Watson & Crick strands are complementary; nucleotides line up on template

according to base pair rules (Watson)

Meselson & Stahl replication is semiconservative; Expt: varying densities of radioactive nitrogen

Meselsen/Stahl Animation

DNA Replication: 500 nucleotides/sec!! Begin at “Origins of replication”

– A specific sequence of nucleotides; 1000s per chromosome Replication forks open to form “replication bubbles”. 2 main stages: Separation & Synthesis Separation:

– Helicase:catalyzes the untwisting of the DNA at the replication fork– Single Strand Binding Proteins: hold the helix open

Synthesis:– DNA polymerase:catalyzes the elongation of new DNA

By the way, DNA has an…. Antiparallel nature: • sugar/phosphate

backbone runs in opposite directions

• one strand runs 5’ to 3’, while the other runs 3’ to 5’

• DNA polymerase only adds nucleotides at the free 3’ end, forming new DNA strands in the 5’ to 3’

direction only

Synthesis: Initiation: Primer (short RNA sequence

is attached first with “primase”) DNA Polymerase then attaches each

new nucleotide to the growing strand using “nucleoside triphosphate”

DNA Pol can only add 5’ to 3’ so… Leading strand: synthesis toward the

replication fork is “continuous (5’ to 3’ direction from the 3’ to 5’ master strand)

Lagging strand: synthesis away from the replication fork is discontinuous.

Okazaki fragments; joined by DNA ligase (must wait for 3’ end to open; again in a 5’ to 3’ direction)

DNA Replication

http://www.johnkyrk.com/DNAreplication.html

DNA Repair

Mismatch repair: DNA polymerase

Excision repair:Nuclease

Telomere ends:telomerase

More Animations!!!

http://www.fed.cuhk.edu.hk/~johnson/teaching/genetics/animations/dna_replication.htm

http://www.stolaf.edu/people/giannini/flashanimat/molgenetics/dna-rna2.swf

http://www.umass.edu/molvis/tutorials/dna/dnapairs.htm

http://207.207.4.198/pub/flash/24/menu.swf