227The Molecular Basis of Inheritance.ppt)€¦ · Chapter 16—The Molecular Basis of Inheritance....
Transcript of 227The Molecular Basis of Inheritance.ppt)€¦ · Chapter 16—The Molecular Basis of Inheritance....
Chapter 16—The Molecular
Basis of Inheritance
I. DNA as the Genetic Material
What was the transforming agent?
Transformation of Bacteria—Griffith Experiment (1928)
Bacteriophages
The Hershey-Chase Experiment (1952)
Conclusion?
DNA, not protein, functions as the genetic material for viruses
Structure of a DNA strand
Structure of a DNA strand
The double helix
Watson, Crick, Franklin, Wilkins, Pauling (1953)
Base Pairing in DNA
Base Pairing in DNA—Chargaff
Chargaff’s Rules—A & T and G & C
are found in equal quantities in DNA
samples (1947)
A pairs with T (2 hydrogen bonds)
G pairs with C (3 hydrogen bonds)
II. DNA Replication & Repair
• Simplified DNA Replication
Basic idea—Watson & Crick 1954
Replication of DNA
base pairing allowseach strand to serveas a pattern for anew strand
Three Models of DNA Replication
Needed to be verified through experimentation
Meselson-Stahl Experiment—(1958)
Meselson-Stahl Experiment—1958
Meselson-Stahl Experiment—1958
� labeled nucleotides of “parent” DNA strands with heavy nitrogen = 15N� labeled new nucleotides with lighter isotope = 14N� replicated strands were found to be half 15N & half 14N
Semiconservative Replication supported
Origins of Replication in Eukaryotes
more than a dozen enzymes & other proteins participate in DNA replication
Helicase—opens DNA helix enabling replication
DNA Strands are Antiparallel
Sugar-Phosphate backbones run in opposite directions
5´ End contains a phosphate group
3´ End contains a hydroxyl (OH) group
Elongating a DNA Strand
DNA Polymerase� Adds nucleotides only to 3´ end (elongation always 5´ → 3´ direction)� Nucleoside-P-P-P links to sugar-P backbone� Losing 2-P provides energy for bonding
Can get energy from:ATP → AMPTTP → TMPGTP → GMPCTP → CMP
Synthesis of Leading & Lagging Strands
Leading strandcontinuous synthesis
(5‘ → 3‘ direction)
Lagging stranddiscontinuous synthesis
Okazaki fragments (still 5‘ → 3‘ direction)
joined by ligase“spot welder”
Priming DNA Synthesis with RNA
DNA polymerasecan only extend anexisting DNAmolecule (Cannotstart a new one)
� short RNA primeris built first onparent DNA strandby primase
� RNA primer laterremoved by another DNApolymerase
Replication Fork
Summary of DNA Replication
DNA Replication Enzymes
Editing & Proofreading DNAAt 1000 bases/second,lots of typos!
Hundreds of DNA repair enzymes exist
Nucleotide Excision Repair
� Nucleases excise
mismatched bases� DNA polymerase fills the
gap� Ligase seals the nick
(reduces error ratefrom 1 in 10,000 to 1in 100 million bases)
The End-Replication Problem
Ends of chromosomesare eroded with eachreplication
Telomeresexpendable, non-codingsequences at ends of DNA
� short sequence of bases
� repeated 100 to 1,000 times
� TTAGGG in humans
� Protects genes from being eroded by replication
� Telomerase enzyme—catalyzes lengthening of
telomeres
“Central Dogma”—Flow of genetic
information within a cell