DNA: The genetic material

1. DNA: The genetic material Chapter 11

2. Discovering the Structure of DNA • DNA is comprised of subunits called nucleotides. • Each DNA nucleotide has three parts: • A central deoxyribose sugar. • A phosphate group. • An organic base.

3. Discovering the Structure of DNA • Nucleotides differ with regards to their bases • Large bases (purines) with double-ring structure • either adenine (A) or guanine (G) • Small bases (pyrimidines) with single rings • either cytosine (C) or thymine (T)

4. Discovering the Structure of DNA • Edwin Chargaff noted that DNA molecules always had equal amounts of purines and pyrimidines. • Chargaff’s rule suggested that DNA had a regular structure. • The amount of A always equaled the amount of T • The amount of C always equaled the amount of G

5. Nucleotides

6. Discovering the Structure of DNA • Rosalind Franklin’s work in 1953 using X-ray diffraction showed that DNA had a regular structure that was shaped like a corkscrew, or helix.

7. Discovering the Structure of DNA • Francis Crick and James Watson elaborated on the discoveries of Franklin and Chargaff and deduced that the structure of DNA was a double helix. • Two strands of DNA bound together by hydrogen bonds between the bases. • Because a purine of one strand binds to a pyrimidine on the other strand to form a base pair, the molecule keeps a constant thickness.

8. How the DNA Molecule Copies Itself • The two strands of DNA that form the double helix DNA molecule are complementary to each other. • Each chain is essentially a mirror image of the other. • This complementaritymakes it possible for DNA to copy itself in preparation for cell division.

9. How the DNA Molecule Copies Itself • The process of DNA replication involves several enzymes: • DNA polymerase • Adds the correct complementary nucleotide to the growing daughter strand, but can only add nucleotides to the 3´ end of an existing strand. • Helicase • Unwinds the DNA to expose the templates. • This creates a replication fork. • DNA ligase • Seals fragments of DNA together.

10. How nucleotides are added in DNA replication Template strand New strand Template strand New strand 3′ HO HO 3’ 5’ 5′ C C P P G G P P Sugar- phosphate backbone T T A A P P P P T T A A P P DNA polymerase III P P C C G G P P 5′ 1′ 4′ P P 2′ 3′ A A OH T 3’ P P P T P P P P P A 5′ A OH 3′ 1′ 4′ 2′ 3′ OH P P 5′ 5′

11. How the DNA Molecule Copies Itself • At the replication fork, a primer must first be added to give a place for DNA polymerase to start. • Using one template, DNA polymerase adds nucleotides in a continuous fashion; this new daughter strand is called the leading strand. 2 Priming the Leading Strand Primase DNA polymerase III 3′ 5′ Helicase 3′ Primer 5′ 3′ Leading strand 5′ Template strands Single-strand binding proteins 1 Unwinding Single-strand binding proteins Parental DNA helix 3′ Helicase 5′ 3′ 5′ Replication fork

12. How the DNA Molecule Copies Itself 4 Priming and Building the Lagging Strand Leading strand 5’ • Because the other template is a mirror image, directionality becomes a problem because DNA polymerase can build a new strand in one direction only. • This second daughter strand is assembled in segments, each one beginning with a primer. • The segments are joined together by DNA ligase to form the lagging strand. Single-strand binding protein 3’ Helicase Okazaki fragment Lagging strand 3’ 5’ 5’ Primer 3’ 3’ 3 Building the Leading Strand 3’ DNA polymerase III DNA polymerase I Primase 5’ DNA polymerase I 3’ DNA polymerase III DNA ligase 5’ Helicase 5’ 3’ Leading strand 3’ Single-strand binding proteins 5’

13. How the DNA Molecule Copies Itself • Before the newly formed DNA molecules wind back into the double helix shape, the primers must be removed and the DNA fragments sealed together. • DNA ligase joins the ends of the fragments of DNA to form continuous strands. http://www.youtube.com/watch?v=TEQMeP9GG6M

14. How the DNA Molecule Copies Itself • Because so much DNA is being replicated in the many cells of the body, there is a potential for errors to occur. • DNA repair involves comparing the daughter strand to the parent DNA template to check for mistakes. • The proofreading is not perfect because mutations are still possible, although rare; however, genetic variation is the raw material of evolution.

15. Mutation • There are 2 main ways in which the genetic message encoded in DNA can be altered. • Mutation • Results from errors in replication. • Can involve changes, additions, or deletions to nucleotides. • Recombination • Causes change in the position of all or part of a gene.

16. Mutation • Mutations can alter the genetic message and affect protein synthesis. • The effect of a mutation depends on the identity of the cell where it occurs. • Mutations in germ-line cells - will be passed to future generations • Important for evolutionary change • Mutations in somatic cells are not passed to future generations but passed to all other somatic cells derived from it.

17. Mutation DNA A G A G T A C T A G G A T C T C A T G A T C C T • Some mutations alter the sequence of DNA nucleotides. • Base substitutionchanges the identity of a base or bases. • Insertionadds a base or bases. • Deletionremoves a base or bases. Serine Histidine Aspartate Proline DNA replication DNA A G A G T A C T A T G A T C T C A T G A T C C T Serine Threonine Histidine Aspartate (a) Base substitution (red) in DNA: changes G to T in the DNA strand and, as a result, proline to threonine in the protein. Normal protein Mutated protein (b) The mutated protein with the amino acid substitute folds differently than the normal protein and its function will most likely be affected.

18. Mutation • If the insertion or deletion throws the reading frame of the genetic message out of register, a frame-shift mutation results. • These are extremely detrimental because the final protein intended by the message may be altered or not made.

19. Mutation • Some mutations affect how a genetic message is organized. • Transpositionoccurs when individual genes move from one place in the genome to another. • Sometimes entire regions of chromosomes may change their relative location or undergo duplication. • This is called chromosomal rearrangement.

20. Mutation • All evolutionary change begins with alterations in the genetic message. • Mutation and recombination provide the raw materials for evolution.

21. Mutation • Chemicals or radiation that cause mutation are called mutagens. • For example, chemicals in cigarette smoke and UV light can cause cancer.