Chapter 6

1. Chapter 6 DNA Structure and Function Part 2

2. Deciphering The Structure of DNA • The DNA molecule is a polymer (or chain) of subunits (or links) called nucleotides. • These nucleotides are composed of only three components: • A five carbon sugar (deoxyribose) • A phosphate group • A nitrogen base (can be adenine (A), guanine (G), cytosine (C), or thymine (T)) (A and G are called purines. C and T are called pyrimidines.) • Though there are only these 3 components that make up the DNA, it is a gigantic molecule. • Chromosomal DNA has a complex structural organization. • Therefore, the puzzle of how the DNA molecule is arranged took more than 50 years to solve.

3. A Nucleotide Adenine Or Guanine Cytosine Or Thymine Deoxyribose Deoxyribose

4. Deciphering the Structure of DNA • In 1950, Erwin Chargaff made two discoveries. • 1: He determined that the amounts of the nitrogen base thymine and the nitrogen base adenine are always the same in all DNA. • He found that the same is true for the amounts of guanine and cytosine. • Therefore, he deduced that, in DNA, A always binds with and G always binds with C. • A=T and G=C • We call this Chargaff’s rule.

5. Deciphering the Structure of DNA • 2: Chargaff discovered that the proportion of adenine and guanine differs among DNA of different species. • This told Chargaff that the composition of DNA varies from one species to another.

6. Deciphering the Structure of DNA: The Race For the Double Helix • Rosalind Franklin, a female British biophysicist , which was rare at the time, took the first clear x-ray diffraction image of DNA as it occurs inside of cells. • X-ray crystallography is a technique in which x-rays are directed though a purified and crystallized substance. • Atoms in the substance’s molecules scatter the x-rays in a pattern that can be captured as an image. • Researchers can then use this image to calculate the size, shape, and spacing between any repeating element in the molecules-all of which are details of molecular structure. • Unbeknownst to her, another British biophysicist, Maurice Wilkins, worked on the same project just down the hall from Franklin.

7. Deciphering the Structure of DNA: The Race For the Double Helix • Using her image of DNA, Franklin was able to decipher the structure of DNA. • In 1952, Franklin gave a presentation of her work on the structure of DNA. • In her presentation, she said that DNA has two chains twisted into a double helix (spiral), with a backbone of phosphate groups on the outside, and nitrogen bases arranged in an unknown way on the inside. • She had even calculated the diameter of the DNA molecule, the distance between its two chains and its bases, the angle of the helix, and the number of bases in each coil of the helix.

8. Deciphering the Structure of DNA: The Race For the Double Helix Rosalind Franklin and her famous x-ray diffraction image of DNA

9. Deciphering the Structure of DNA: The Race For the Double Helix

10. Deciphering the Structure of DNA: The Race For the Double Helix • While Franklin began to write a paper to publish her work so that she could be recognized for her findings, Wilkins began to review her image of DNA with American biologist, James Watson. • Watson and a British biophysicist names Francis Crick had been working on the molecular structure of DNA themselves. • They had already hypothesized that the secondary structure of the DNA molecule might be a helix. • They had also attempted to build a DNA model with scraps of metal and wire “bonds”. • They struggled with and argued about the size, shape, and bonding requirements of the nucleotides that make up DNA. • They had even asked chemists to help them identify possible bonds that might be present in DNA that they might have overlooked.

11. Deciphering the Structure of DNA: The Race For the Double Helix • After Wilkins and Watson reviewed Franklin’s image, Watson and Crick read a report containing her unpublished data. • Franklin’s DNA image and data provided Watson and Crick with the information they needed to complete their DNA model in 1953, revealing the true structure of the DNA molecule.

12. Deciphering the Structure of DNA: The Race For the Double Helix Crick Watson

13. Deciphering the Structure of DNA: The Race For the Double Helix • Watson and Crick were then the first to publish a theoretical model of the structure of DNA. • Wilkins research paper on his work with DNA structure was the second to be published. • Rosalind Franklin’s work was the third paper to be published in a series of articles about the structure of DNA in Nature. • Rosalind Franklin died at the age of 37 due to ovarian cancer, probably caused by extensive exposure to x-rays. • Since the Nobel Prize is not given posthumously, Franklin did not get to share in this honor bestowed upon Watson, Crick, and Wilkins in 1962 for their work on the discovery of the structure of DNA.

14. Deciphering the Structure of DNA: The Race For the Double Helix A 1962 photo shows Nobel Prize winners (from left): Maurice Wilkins (medicine), Max F. Perutz (chemistry), Francis Crick (medicine), John Steinbeck (literature), James Watson (medicine) and John C. Kendrew (chemistry). Not pictured are winners Linus Pauling (peace) and Lev Landau (physics).

15. The Double Helix • Watson and Crick said that DNA is composed of two strands (or chains) of nucleotides. • They said that these two strands run in opposite directions. They are said to be antiparallel. • These two strands are coiled into a double helix (or spiral). • Bonds between the sugar of one nucleotide and the phosphate group of the next nucleotide (called phosphodiester bonds) form the “backbone” of the DNA molecule. • Hydrogen bonds between the nitrogen bases on the inside of the DNA molecule hold the two DNA strands together. • Only two kinds of base pairings occur in DNA: A binds to T and G binds to C, just as Chargaff had said in his first rule. • Due to this complementary base pairing, the two DNA strands are said to be complementary to one another.

16. The Double Helix

17. Patterns of Base Pairing • Just the two kinds of base pairing (A=T and G=C) give rise to the enormous diversity that we see in all living things on Earth. How is this possible? • The diversity that we see among living things is due to the fact that, even though there are only four possible bases in DNA, the order in which these bases occur varies greatly from one species to the next. • The DNA sequence, or the order in which one base pair follows the next in DNA, explains Chargaff’s second rule. • The information encoded by this DNA sequence is responsible for all traits, seen and unseen, that define species and distinguish individuals from one another.

18. DNA Sequence = Genetic Information= Diversity

19. DNA Replication • Before a cell divides, it must replicate (or make an identical copy) its DNA so that each new cell that is produced will receive DNA. • During DNA replication, • 1st- an enzyme called DNA helicase breaks the hydrogen bonds holding the two DNA strands together, effectively “unzipping” and separating the two DNA strands.

20. DNA Replication • 2nd- Another enzyme, called DNA polymerase, assembles a complementary strand of DNA (called a daughter strand) on each original (parent) strand of DNA. • The DNA polymerase uses each parent as a template (or blueprint) upon which to construct the new, daughter strands. • The base sequence of the daughter strand is complementary to that of the parent strand because DNA polymerase must follow base-pairing rules. • In this way, two identical copies of DN are produced, ensuring that each new cell will get identical DNA.

21. DNA Replication

22. DNA Replication • 3rd- The enzyme, DNA ligase, seals any gaps that remain in either of the DNA strands in each new DNA molecule, producing two new continuous DNA strands. • Then the DNA molecules recoil into a double helix. • Because each new DNA molecule consists of one newly synthesized strand (new) and one original (parent) strand, DNA replication is said to be semi-conservative, meaning that part of the original DNA molecule is conserved in the new DNA molecules.

23. DNA Replication is Semi-Conservative Original

24. Checking For Mistakes • DNA replication is not always perfectly accurate. Mistakes can and are made. These mistakes are called mutations if they are not corrected and become permanent. • Sometimes the wrong nucleotide/base is added to the growing, newly synthesized strand. Sometimes nucleotides/bases are lost or extra ones are added. • Errors may also be caused by exposure to radiation or toxic chemicals because it is difficult for DNA polymerase to add nucleotides to a damaged parental DNA strand. • However, most of the time, DNA repair mechanisms fix the mistakes that are made by replacing damaged or mismatched nucleotides.

25. Checking for Mistakes • Most errors during replication happen because DNA polymerase adds nucleotides to the newly synthesized strand so quickly-up to 1,000 bases per second. • Luckily, however, DNA polymerase proofreads its work and correct mismatches immediately. • In the case that DNA polymerase fails to correct a mistake that it has made, other mechanisms usually stop the cell from dividing.

26. Checking for Mistakes • If proofreading and repair mechanisms fail, and the cell is allowed to divide with the mistake still present, then the error in the DNA becomes permanent and is called a mutation- or a permanent change in the DNA. • These mutations can alter the information encoded by the DNA, possibly resulting in harm to the organism. • Mutations are the original source of variation of traits (for example, skin color). Therefore, they are the raw material of evolution.

27. Mistakes During DNA Replication