DNA - The Genetic Material

Scientist and Their Contributions:

    1869 - Freidrich Miescher (Swiss biochemist) - isolated material from the nucleus.  He called nuclein
                Other Scientists - high in phosphorus and acidic - became known as nucleic acid

            2 Kinds - DNA - Deoxyribonucleic acid
                            RNA - Ribonucleic acid

    1928 - Frederick Griffith (English bacteriologist) - determined that a genetic material exists by the
                transformation of a non-pneumonia-causing bacterium into a pneumonia-causing bacterium.
He injected mice with bacteria in his study.

                    R strain (uncoated) bacteria - did not kill mice
                    S strain (coated) bacteria - killed mice
                    heat-killed S bacteria - did not kill mice
                    heat-killed S mixed with living R - killed mice - conclusion - living R picked up genetic
                        material from the dead S.

    1944 - Oswald Avery, Colin Maclead. and Maclyn McCarty (Rockefeller Institute in New York) -
                - identified the tranforming genetic material as DNA.

    1952 - Alfred Hershey and Martha Chase - conformed that DNA is the genetic material using virus
                    and bacteria.

                    Radioactively labeled the DNA of virus which then infected bacteria cells.  The bacteria
                    cells were observed to contain radioactivity indicating that the viral DNA entered the cell
rather than the protein of the virus.

    1920's - P. A. Levene (biochemist) - DNA is made up of the following chemical groups:
                        deoxyribose - a 5-carbon sugar
                        a phosphate group
                        four kinds of nitrogen bases - purines -adenine and guanine
                                                                     pyrimidines - cytosine and thymine

    ~1950 - Rosalind Franklin and Maurice Wilkins (Oxford University) -
                            X-ray images of DNA crystals - helix shape.

    1953 - James Watson (American biochemist) and Francis Crick (English physicist)
                    in Cambridge, England

                    Described the structure of DNA as a double helix - like a twisted ladder:

                    sides of ladder are made up of alternating phosphate groups and deoxyribose
                    rungs of ladder are made up of paired nitrogen bases:

                                                adenine - thymine
                                                cytosine - guanine

DNA Replication - making a copy of the DNA

    This must occur before a cell divides into two cells so that both daughter cells receive a complete
copy of the DNA.

    DNA polymerase - unzips the DNA by breaking hydrogen bonds between nitrogen bases.
     DNA nucleotides are added along each separated strand of DNA until two identical molecules
     of DNA are formed.  Each will have a new and old strand of DNA nucleotides, therefore
     DNA replication is said to be semi-conservative.

How is DNA the genetic material?

    In the sequence of nitrogen bases, DNA contains the instructions to make proteins.  The proteins
    an organism makes determines that organism's traits.  Every cell of an organism holds a complete
    copy of the DNA in its nucleus.  Humans have 46 chromosomes, each of which contains one
    long molceule of DNA.  Along one molecule of DNA several different protein recipes (genes)
    are found.  Since DNA can not leave the nucleus and proteins are made by ribosomes in
    the cytoplasm of the cell, the protein instructions must be delivered to the cytoplasm by a messenger.
    This is the role of mRNA which is a movable copy of the DNA.  The ribosome reads the mRNA
and puts together the protein using amino acids which are delivered to the ribosome by tRNA molecules.

            Summary of Protein synthesis:    DNA --(transcription)----> mRNA ---(translation)---> protein

            Transcription - RNA polymerase unzips the DNA and build a mRNA along one of the DNA strands.
                        The nitrogen bases of RNA nucleotides bind to the nitrogen bases of that template strand:

                                      DNA bases        RNA Bases
                                            A       binds to     U
                                            T       binds to      A
                                            C       binds to     G
                                            G       binds to     C

                        The RNA polymerase connects all of the RNA nucleotides by forming a bond between
                        the ribose of one RNA nucleotide to the phosphate group of the next nucleotide.  Once the
                        entire gene is transcribed into mRNA the mRNA peals off of the template strand of DNA
                        and the DNA molecule zips back up.

                        RNA processing - often some alteration of the mRNA occurs before it travels to the cytoplasm.

                            intron - non-coding regions - cut out
                            exons - coding regions - joined together

                            also a guanosin cap and poly A tail are added:

                                G- cap - AUGCCCGUUGCGUACGAAUCGUAAAAAAAAAAAAA (poly-A tail)

            Translation - building of the protein.
                            Three kinds of RNA are involved:
                                        mRNA (messenger) - carries the information on amino aicd sequence of the protein
                                        rRNA (ribosomal) - part of the ribosome structure togther woth proteins
                                        tRNA (transfer) - delivers amino acid to the ribosome

                                Genetic Code - every 3 nitrogen bases on the mRNA is called a codon.  A codon codes
                                        or calls for a certain amino acid (building block of protein).  We can use a codon
                                        chart to figure out what each of the different codons means.  Since there are 4
                                        different nitrogen bases which could be in three separate positions in the codon,
                                        there are 4 x 4 x 4 = 64 possible codons.  But there are only 20 different amino
                                        acids.  Some of the codons code for the same amino acid.  This prevents some
                                        mutations (changes in the DNA base sequence) from causing changes in the
                                        protein.  A changed codon may still code for the same amino acid.  There is
                                        one start codon (AUG) and three stop codons (UAA, UAG, UGA).

                                  A ribosome joins with the beginning of mRNA and waits until a tRNA with the
                                    appropriate amino acid (the one coded for by the codon it is reading) wanders by.
                                    The tRNA has a "tag" called the anti-codon that is complementary to the codon.
                                    Only the tRNA that carries the correct amino acid would have the anti-codon that
                                     could bind to the codon that codes for the amino acid that it is carrying.
                                     For example:  The mRNA codon AUG codes for the amino acid methionine
                                     which will be delived by a tRNA molecule with anti-codon UAC.

                                  The ribosome travels the length of the mRNA reading 2 codons at a time as tRNA
                                    molecule deliver the correct amino acids.  The ribosome joins the amino acids
                                    together with peptide bonds.  When the ribosome encounters a stop codon it
                                    becomes detached from the mRNA and the chain of amino acids (protein).