The Molecular Basis of Inheritance Who are these two famous characters of science?

Searching for Genetic Material Mendel (1865): Inheritance

Searching for Genetic Material What are chromosomes made of? T.H. Morgan (1910): genes linked on chromosomes Chromosomes are made of DNA and proteins DNA and proteins are the two candidates for the genetic material

Searching for Genetic Material Griffith(1928): bacterial work- streptococcus pneumoniae

Searching for Genetic Material Griffiths’ conclusion: Transformation: change in genotype and phenotype due to assimilation of external substance (DNA) by a cell

Searching for Genetic Material Avery and team(MacLeod and McCarty)(1944): transformation agent was DNA

Searching for Genetic Material Hershey and Chase(1952): determine that DNA is the hereditary material and not proteins:

DNA Structure Chargaff(1950): Chargaff rules: A= T, C= G found “peculiar regularity” in the ratios of nucleotide bases within a single species: A = 30.3% T = 30.3% C= 19.9% G = 19.5% Chargaff rules: A= T, C= G

Watson & Crick(Wilkins, Franklin)(1953): The Double Helix

The Double Helix: Basic Unit of Nucleic Acids = nucleotide Sugar/ phosphate backbone Nitrogen base

Sugar/phosphate backbone: 5 carbon sugar = ribose Phosphate group Phosphodiester bond

Nitrogenous bases: In DNA there are four(make up the interior of the molecule): Adenine Thymine Cytosine Guanine Two groups: Purines: double ringed structures Adenine and Guanine Pyrimidines: single ringed structures Thymine and Cytosine

Polynucleotide directionality: 5’ to 3’ 5’ with the phosphate group 3’ with the –OH group

Double strands: Inward facing nitrogen base will pair with their complementary base A will pair with T (two H- bonds) G will pair with G (three H- bonds) A double ringed structure will always pair with a single ringed structure to maintain width.

Antiparallel: DNA strands are oriented in the opposite directions

Other forces: Van der Waals attractions play a role in holding the DNA molecule together

The Double Helix:

DNA Replication

Watson and Crick: Proposed the semiconservative model of DNA replication:

Meselson & Stahl: semiconservative replication

Enzymes: Helicase, DNA polymerase, Primase, DNA ligase Topoisomerase

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Replication Origin: Sites where DNA replication begins Prokaryotes: one origin Replication proceeds in two directions Humans: hundreds maybe thousands of origins

Replication bubbles and Replication Forks; Replication bubble: unwinding and separation of the DNA strand Replication fork: Y- shaped region at each end of the bubble

Strand elongation and directionality: Elongation catalyzed by DNA polymerase E. coli bacteria adds nucleotides at a rate of 500/sec Humans add nucleotides at a rate of 50/sec Nucleoside triphosphate:

Strand elongation and directionality Antiparallel elonagation: 5’ – 3’ direction Leading strand Lagging strand Okazaki fragments E. coli fragments: 1000- 2000 nucleotides Human fragments: 100 -200

Primers: How many primers are needed for the leading strand? How many primers are needed for the lagging strand?

DNA Replication Continued: DNA replication ensures continuity of hereditary information:

DNA Replication continued: 1. Enzymes of DNA replication work as part of a large complex: 2. Replication process is probably a stationary process DNA polymerase “reels- in” the parent DNA Lagging strand may may be looped

Problems with replication: Incorrectly paired nucleotides Error rate: 1 out of every 100,000 base pairs DNA polymerase proof reads each nucleotide Incorrectly paired nucleotides are immediately removed and replaced 1 out of 10 billion

Problems with replication: Mismatch pair: Repaired by the action of nuclease(one of many different DNA repair enzymes) Removes nucleotides damaged by chemicals or the environment

Problems with replication: End replication repair:

Telomeres and Telomerase: Telomeres= nucleotide sequences at the ends of the DNA molecule Contain a repeated unit TTAGGG Do not contain genes No nucleotides added Protects the molecule from the replication process Triggers apoptosis May contribute to the aging process

Telomerase: Catalyzes the lengthening of the telomeres in eukaryotic germ cells