Lecture 3 DNA Structure

Discovery: • & (1953) ▪ Created the first accurate model of DNA ▪ Won the Nobel Prize Watson and Crick reached to this result through studies of previous scientist as Frederick Griffith (proof that DNA is genetic material), Chargaff (rules of A-T, G-C), and (DNA X-ray diffraction data) Early Work: • Friedrich Miescher, 1869, first isolates a substance from the nucleus of cells that he calls “nuclein.” His student, Richard Altmann, calls the substance “nucleic acid.” • Biochemists identify two types of nucleic acids, later called RNA and DNA. • In 1929, Phoebus Levine at the Rockefeller center identifies the four bases of DNA. • Though early researchers knew that DNA was found in chromosomes, they doubted that it was the hereditary material. There were only four bases. How could for bases code for all sorts of proteins? • Some researchers, including Linus Pauling, thought that the protein also found in chromosomes was probably the hereditary factor. Frederick Griffith • In 1928, Frederick Griffith carried out experiments on bacteria in mice. • Discovery: something in heat-killed virulent bacteria could be transferred to harmless bacteria and make it virulent. • Avery continued working with Griffith’s findings in hope of discovering what factor in bacteria carried the trait of . • Isolated proteins, carbohydrates, nucleic acids and applied them to non- virulent bacteria. Only nucleic acids (DNA) caused a change. • Chargaff studied DNA itself, in hopes of providing some clues about its structure. • Discovered that there are always equal amounts of the bases Adenine and Thymine, and equal amounts of Cytosine and Guanine. • Chargaff proposed that these bases pair with one another in some way. Wilkins and Franklin

Page • Rosalind Franklin and Maurice Wilkins worked with X-ray crystalography to find more clues about the structure of DNA. 1

• Franklin’s X-ray images suggested a helical structure. Watson and Crick • James Watson and Francis Crick were also working on discovering the structure of DNA. • Applied Chargaff’s rule, assumed that A always pairs with T, C with G. • Watson was not entirely convinced of the helical structure that Franklin had suggested, and his critique of her work led her to doubt herself. • Wilkins consulted with Watson and Crick. Without Franklin’s knowledge, he handed them the data that he and Franklin had worked on. • Watson immediately recognized the significance. He and Crick went to work on a model of DNA. DNA • DNA Is a Structure That Encodes Biological Information. • DNA is abbreviation of Deoxyribo-Nucleic Acid • DNA is a double helix – this makes DNA look like a “twisted ladder”. • Each molecule of DNA is composed of a “backbone” on the outside and bases that point towards the middle of the molecule. DNA Structure • Nucleic acid is composed of a long polymer of individual molecules called nucleotides . Nucleotide Structure • Each nucleotide is composed of: 1. Nitrogenous base, 2. a sugar molecule, and 3. a phosphate molecule.

Nucleotide vs Nucleoside • Nucleoside = nitrogenous base + sugar • Nucleotide = nitrogenous base + sugar + phosphate Page

• When phosphate is added to nucleoside it becomes a nucleotide. 2

BASE NUCLEOSIDE DEOXYNUCLEOSIDE Adenine Adenosine 2-deoxyadenosine Guanine Guanosine 2-deoxyguanosine Cytosine Cytodine 2-deoxycytodine Uracil Uridine Not usually found Thymine Not usually found 2-deoxythymidine

1. Nitrogenous bases • The four nucleotides found in DNA differ only in their nitrogenous bases. • There are two types of nucleotides, purines and pyrimidines. • Purines have two rings in their structure, while pyrimidines have just one. • The purines include: • Adenine • Guanine • The pyrimidines include: • Cytosine • Thymine (only in DNA) • Uracil (only in RNA). Sugar: • DNA  Deoxyribose. • RNA  Ribose.

Phosphodiester bonds Nucleotides are linked by phosphodiester bonds between the 3' and 5‘ carbons of adjacent sugars

Sugar-Phosphate backbone Page • The alternating phosphate and sugar residues make the backbone of the DNA

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strand.

Double Helix • The DNA molecule is composed of two chains of nucleotides arranged in a double helix. Two Chains • The two chains being held together by hydrogen bonds between the nitrogenous bases which point in towards the center of the helix. Direction • The DNA chain end terminated by the 5' carbon atom of the sugar molecule is referred to as the 5' end (5 prime), and the end terminated by the 3‘ carbon atom is called the 3' end (3 prime). Antiparallel strands: • In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand • In the DNA duplex the 5' end of one strand is opposite the 3' end of the other. Base pairing • The arrangement of the bases in the DNA is not random: • G in one chain always pairs with C in the other chain. • A always pairs with T • i.e. this base pairing forming complementary strands. • This base pairing means that the two DNA strands are complementary strands. Types of Nucleic acid: There are two different types of nucleic acid: • Ribonucleic acid (RNA): contains the sugar ribose (five carbon sugar) • Deoxyribonucleic acid (DNA):, contain the five carbon sugar deoxyribose. RNA vs. DNA • RNA contains the sugar ribose; DNA contains deoxyribose. • RNA contains the base uracil; DNA contains thymine instead. • RNA is usually single stranded; DNA is usually double stranded. • RNA is short: one gene long at most; DNA is long, containing many genes. DNA and RNA: • In Deoxyribose, the hydroxyl group at the 2' position of the ribose sugar is replaced by a hydrogen (i.e. an oxygen atom is lost, hence 'deoxy'). • DNA and RNA both contain the purine bases adenine and guanine and the pyrimidine cytosine • Thymine occurs only in DNA and uracil is found only in RNA. • DNA and RNA both contain the purine bases adenine and guanine and the pyrimidine cytosine • Thymine occurs only in DNA and uracil is found only in RNA.

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Comparison between DNA and RNA

DNA RNA Sugar Deoxy ribose Ribose Bases Adenine, Adenine, Guanine, Guanine, Cytosine, and Cytosine, and Thymine Uracil Number of Two One Strand Strand length Long Short

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