Molecule of Inheritance - DNA

Molecule of Inheritance - DNACh 16MorganGenes are on chromosomes

Chromosomes are made of DNA & protein

What is the molecule of inheritance? What are genes made of?1928 - Transforming FactorFrederick Griffith, a British medical officer, discovers that genetic information can be transferred from heat-killed bacteria cells to live ones, in a process called transformation.

Griffiths Experiment - used pneumonia bacteria1944 - DNA is the inheritance moleculeOswald Avery and his colleagues Maclyn McCarty and Colin MacLeod, repeat Griffiths work, trying to identify which molecule is responsible for transformation. They identify Griffith's transforming agent as DNA.

Averys Experiment1952Alfred Hershey and Martha Chase experiment with the T2 virus, confirming that DNA is the genetic material (vs. protein).

What is the structure of DNA?1909, 1929 - Nucleotides 1909 and 1929 - In 1909, Phoebus Levene discovered ribose, a sugar present in genetic material. Later in 1929, he discovered deoxyribose and nucleotides (adenine, guanine, cytosine, and thymine), recognizing the significance of phosphate-sugar bases in the structure of DNA. DNA is made of nucleotides

1949 - Base PairingErwin Chargaff finds that the amount of adenine equals the amount of thymine, and the amount of guanine equals the amount of cytosine in DNA from every species.A = T, C = G

The two strands of the DNA molecule run antiparallelOne goes from 5-3, the complementary strand goes from 3-5

1951Rosalind Franklin, Maurice Wilkins, and Raymond Gosling take X-ray diffraction pictures of DNA. From Rosalind Franklins pictures, she determines that DNA has a helical shape.

1953 - Double HelixJames Watson and Francis Crick discover the double helix molecular structure of DNA.

What is the structure of the DNA molecule?James Watson and Francis CrickBuilt models of nucleotides

Determined how nucleotides were arranged in molecule:Sugar phosphate backboneHeld together by Covalent bonds

Nitrogenous bases paired in middle a purine is always paired with a pyrimidineHeld together by Hydrogen bonds

16The DNA double helix is anti-parallel, which means that the 5' end of one strand is paired with the 3' end of its complementary strand (and vice versa).

1962Francis Crick, James Watson, and Maurice Wilkins receive the Nobel Prize for determining the molecular structure of DNA.

In 1958, Rosalind Franklin died at age 37. The Nobel prize is not given posthumously.James Watson about discovering the structure of DNA (video - 1:42 min)

http://www.hhmi.org/biointeractive/dna/video.html

DNA ReplicationIt has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material. Watson & Crick

Replication making DNA from existing DNA

Semiconservative replication each daughter strand consists of an old strand (from parent molecule) and a newly made strand

(Meselsohn-Stahl experiment)

http://highered.mcgraw-hill.com/olc/dl/120076/bio22.swf

DNA replication

Energetics of DNA replicationSecond law of thermodynamics Systems go towards more disorder

DNA is creating order out of chaos, so does it go against the second law?

DNA + dNTP DNA (with new nucleotide) + P-P DNA (with new nucleotide ) + 2 P

Rather than adding nucleotides, DNA is synthesized from nucleoside triphosphates a sugar + base + 3 phosphate groups

As they are added, the 2 phosphates are cleaved, and then split into two inorganic phosphates.

This is energetically favorable- an exergonic reaction coupled with the polymerization.

Directionality of DNADNA can only be synthesized in the 5 3 direction

Additional nucleotides are added to the 3 end

This results in a problem when replicating DNA one new strand can be synthesized continuously, the other has to be synthesized in segments

DNA replication fork:http://highered.mcgraw-hill.com/olc/dl/120076/micro04.swf

How nucleotides are added to DNA strand:http://highered.mcgraw-hill.com/olc/dl/120076/bio23.swf

Proteins involved in replicationHelicase unwinds DNAPrimase makes RNA primer (short sequence of 5-10 RNA bases)Single strand binding proteins hold DNA strands apartDNA polymerase III can only add to existing 3 strand, adds nucleotides to 3 end of DNAReads 3-5, builds 5-3

Proteins involved in replicationDNA polymerase I removes RNA primer, replaces w/DNADNA ligase joins ends of DNA from primer or Okazaki fragmentsTopoisomerase keeps DNA from rewinding

DNA replicationhttp://www.dnatube.com/video/335/Animated-DNA-Replication

DNA wrapping & replicationhttp://www.youtube.com/watch?NR=1&feature=fvwp&v=OjPcT1uUZiE

Replication Bubble

Replication occurs on either side- note leading & lagging strandsDNA repairsMismatch repair

http://www.youtube.com/watch?v=7xc1lmWDiS4

DNA damage

Thymine dimerhttp://vimeo.com/81294755

Nucleotide excision repair Telomeres & Telomerasehttp://www.youtube.com/watch?v=AJNoTmWsE0s

Without Telomerase cells reach limit of divisions, 50-70

Telomerase found in embryonic cells, adult cells that need to divide regularly (i.e. male germ cells) not in most somatic cells.

Telomerase activation has been found in 90% of tumors cells are immortal, can divide forever. . .