Principles of Biology Lecture Notes Fall, 2006 MOLECULAR BASIS OF INHERITANCE The Search for the Genetic Material •The role of DNA in heredity first worked out by studying Evidence That DNA Can Transform Bacteria •Frederick Griffith - Streptococcus pneumoniae –bacterium causes pneumonia in mammals –a pathogenic strain & a nonpathogenic strain Evidence That Viral DNA Can Program Cells •Additional evidence for DNA as the genetic material •heat-killed remains of pathogenic strain mixed with living cells of the nonpathogenic strain, some living cells became pathogenic •He called the phenomenon •Now defined as a change in • due to The Hershey and Chase experiment studying bacteriophages a virus that infects bacteria widely used as tools by researchers in molecular genetics Fig 16.4 Additional Evidence That DNA Is the Genetic Material Prior to the 1950s, it was already known that DNA Is a polymer of , each consisting of components: Erwin Chargaff DNA base composition from one species to the next molecular diversity among diverse species made DNA a more credible candidate for the genetic material Also found all species: Challenge: How Does DNA Structure Produce Its Role in Inheritance? Maurice Wilkins & Rosalind Franklin study molecular structure by Franklin from her picture of DNA molecule concluded • DNA =2 antiparallel sugar-phosphate backbones • nitrogenous bases paired in the molecule’s interior • specific base pairing: A-T& G-C Watson and Crick: Franklin’s X-ray crystallographic images of DNA deduced that DNA was a double helix Specific pairing dictated by the structure of the bases Each base pair forms a different number of hydrogen bonds A & T form 2 H bonds; C & G form 3 H bonds 106736912 2/16/2016 Complementary Base Pairing A & T form bonds C & G form bonds Sugar = “Function” of each C in the sugar: C1 – C4 C2 – C5 – C3 – Complementary Base Pairing •Is The Mechanism of Base Pairing to a Template Strand •Since the two strands of DNA are complementary –Each strand acts as a for •Occurs in both –REPLICATION = –TRANSCRIPTION = NOTE: Strand = DNA Molecule DNA Replication: - Overview •In DNA replication –The parent molecule , and new daughter strands are built based NOTE: molecule = DNA double helix DNA Replication: : Semiconservative I –Each of the two new daughter molecules will have strand, derived from –and one newly made strand DNA Replication: : Semiconservative II Conclusion from Meselson & Stahl experiment Fig Replication is DNA Replication: : Semiconservative III Experiments performed by Meselson and Stahl Supported the DNA Replication: Origins of Replication •Replication begins at special sites called –Eukaryotic chromosome – 106736912 Fig: : model of DNA replication , where the of replication origins 2/16/2016 DNA Replication: Elongation •Elongation of new DNA at a –Is catalyzed by , which add to the end of a growing strand DNA Replication: Antiparallel Elongation •Effect on replication of the antiparallel structure of the double helix •DNA polymerases Only adds nucleotides to free end of a growing strand •Along one template strand of DNA, the leading strand DNA polymerase III can synthesize a complementary strand , moving toward •Along the other new strand of DNA, the lagging strand DNA polymerase III must work in the direction the replication fork Lagging strand is synthesized as then , which are by DNA Replication: Leading Strand & Lagging Strand •Synthesis of leading and lagging strands during DNA replication Fig: DNA Replication: Priming DNA Synthesis DNA polymerases cannot the synthesis of a polynucleotide They can only The initial nucleotide strand is an Only primer is needed for synthesis of the leading strand But for synthesis of the lagging strand, must be primed Fig DNA Replication: Other Proteins That Assist DNA Replication Fig: Helicase Topoisomerase single-strand binding protein DNA Replication A summary • • Fig The DNA Replication Machine as a Stationary Complex – The various proteins that participate in DNA replication – Form a single large complex, a DNA replication “machine” The DNA replication machine – Is probably stationary during the replication process 106736912 2/16/2016 DNA Replication: Replicating the Ends of DNA Molecules •The ends of eukaryotic chromosomal DNA get shorter with each round of replication •Eukaryotic chromosomal DNA molecules Have at their ends nucleotide sequences, called that postpone the erosion of genes near the ends of DNA molecules DNA Replication: Replicating the Ends of DNA Molecules •The ends of eukaryotic chromosomal DNA get shorter with each round of replication •If the chromosomes of germ cells became shorter in every cell cycle essential genes would eventually be missing from the gametes they produce An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells DNA Replication: Proofreading and Repairing DNA DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides In mismatch repair of DNA Repair enzymes correct errors in base pairing In nucleotide excision repair Enzymes cut out and replace damaged stretches of DNA 106736912 2/16/2016