Chapter 8 DNA Structure and Function Prepared by Wendi A. Roscoe, Fanshawe College Copyright © 2020 Nelson Education Ltd. 1 The Central Dogma of Gene Expression Copyright © 2020 Nelson Education Ltd. 2 8.1 DNA Structure • Nucleic acids are very long polymers that are made up of nucleotides. • Each nucleotide has three parts. 1. A five-carbon sugar (ribose or deoxyribose) 2. A phosphate group 3. An organic, nitrogen-containing base • What are the five nucleotides? • Which one is only found in RNA? Copyright © 2020 Nelson Education Ltd. 3 8.1 DNA Structure • • What do DNA and RNA stand for? What are the three differences between DNA and RNA? 1. DNA has thymine; RNA has uracil. 2. DNA is double-stranded; RNA is single-stranded. 3. DNA has deoxyribose; RNA has ribose. Copyright © 2020 Nelson Education Ltd. 4 8.1 DNA Structure • The structure of DNA is a double helix. • Only two base pairs are possible. • Adenosine (A) pairs with thymine (T). • Cytosine (C) pairs with guanine (G). • The bond holding a base pair together is a hydrogen bond. • The sugar-phosphate backbone consists of phosphodiester bonds. Copyright © 2020 Nelson Education Ltd. 5 8.1 DNA Structure Copyright © 2020 by Nelson Education Ltd. 6 8.1 DNA Structure • The structure of DNA helps it to function. • The hydrogen bonds of the base pairs can be easily broken to unzip the DNA so that information can be copied. • Each strand of DNA is a mirror image, so the DNA contains two copies of the information. • Having two copies means that the information can be accurately copied and passed to the next generation. Copyright © 2020 Nelson Education Ltd. 7 8.1 DNA Structure • Nucleotides differ with regard to their bases. • Large bases are called purines and have a double-ring structure: adenine and guanine. • Small bases are called pyrimidines and have a single-ring structure: cytosine and thymine. • Edwin Chargaff noted that DNA molecules always have equal amounts of purines and pyrimidines. • Chargaff’s rule suggests that DNA has a regular structure. • The amount of A always equals the amount of T. • The amount of C always equals the amount of G. Copyright © 2020 Nelson Education Ltd. 8 8.1 DNA Structure • Purines: adenine and guanine (double-ring structures) • Pyrimidines: cytosine and thymine (single-ring structures) Copyright © 2020 Nelson Education Ltd. 9 8.1 DNA Structure The carbons on ribose and deoxyribose are numbered 1 to 5. Copyright © 2020 by Nelson Education Ltd. 10 8.1 DNA Structure Copyright © 2020 Nelson Education Ltd. 11 8.1 DNA Structure Copyright © 2020 Nelson Education Ltd. 12 8.1 DNA Structure • ATP is a nucleoside triphosphate that is produced in all cells and is the primary source of energy for all cell functions. • GTP can also be used as energy in cells. Copyright © 2020 Nelson Education Ltd. 13 8.1 DNA Structure: Nucleosides • Our diet is the source of nucleosides in our cells that can be made into nucleotides for DNA replication or used for the transcription of RNA molecules. • All plant and animal cells contain DNA and RNA. • We have enzymes in our digestive tract that break down nucleic acids into individual nucleosides. Copyright © 2020 Nelson Education Ltd. 14 8.1 DNA Structure: Telomeres • A telomere is a region of repetitive DNA at the end of every chromosome. • Telomeres protect the ends of the chromosome from deterioration. • The telomere regions shorten during DNA replication because there is a gap left after the removal of the first 5′ end primer. • Telomeres get shorter after every cell division. • This is what causes our cells to have a specific lifespan, and this is why we age. Copyright © 2020 Nelson Education Ltd. 15 8.1 DNA Structure: Telomeres • Telomeres that shorten faster than normal are linked to degenerative diseases such as cancer and Alzheimer’s disease. • Telomeres shorten with each cell division; anything that causes an increase in cell division will also increase the rate of telomere shortening. • Chronic inflammation (eg. stress) causes increased cell division; inflammation is linked to degenerative diseases partly because of telomere shortening. • It has also been shown that high levels of stress increase the rate of telomere shortening. Copyright © 2020 Nelson Education Ltd. 16 8.1 DNA Structure: Telomeres Copyright © 2020 Nelson Education Ltd. 17 8.1 DNA Structure: Telomeres • Prokaryotes do not have telomeres because their DNA is circular. • An enzyme called telomerase is found in stem cells and germ cells (which give rise to gametes), which replaces the telomere sequences. • Cancer cells also produce telomerase, which is why cancer cells are immortal (i.e., they never die). • This is also why a “telomerase drug” can’t be used to prevent aging. Copyright © 2020 Nelson Education Ltd. 18 DNA Trivia • The average length of a single chromosome is 2 inches. • We have 46 chromosomes in each cell. • The total length of DNA per cell is about 2.3 metres. • All DNA in every cell of our body (about 50 trillion cells) would stretch to about 300 000 000 metres—it could reach the moon! Copyright © 2020 Nelson Education Ltd. 19 8.2 DNA Replication • 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. • The hydrogen bonds that hold the base pairs together are weak bonds and, therefore, easy to separate. • What is the complementary strand of this DNA sequence: 5′ GGTACCAGT 3′? Copyright © 2020 Nelson Education Ltd. 20 8.2 DNA Replication Copyright © 2020 Nelson Education Ltd. 21 8.2 DNA Replication Copyright © 2020 Nelson Education Ltd. 22 Watch video animation: Copyright © 2020 Nelson Education Ltd. 24 8.2 DNA Replication Copyright © 2020 Nelson Education Ltd. 25 8.2 DNA Replication 8.2 DNA Replication 1. Replication begins at a point of origin; in eukaryotes there are many points of origin. 2. An enzyme called helicase unwinds the DNA. 3. The section where the DNA is unwound is called the replication fork. 4. Single-strand binding proteins stabilize the separated strands of DNA. 5. DNA polymerase moves along each strand of unwound DNA and adds the correct complementary nucleotides. Copyright © 2020 Nelson Education Ltd. 27 8.2 DNA Replication 6. DNA polymerase can only add new nucleotides to an existing strand of DNA. 7. Therefore, primase adds a small fragment of RNA (an RNA primer) to the initially separated DNA. 8. The RNA primer is complementary to the DNA, and this is later replaced with DNA. Copyright © 2020 Nelson Education Ltd. 28 8.2 DNA Replication 9. Since the two DNA strands are antiparallel, one strand is oriented as 5′ to 3′ and the other strand is oriented as 3′ to 5′. 10. Polymerase can only add new nucleotides to the 3′ end of the new DNA strand; this is called the leading strand. 11. The opposite strand is called the lagging strand. Copyright © 2020 Nelson Education Ltd. 29 8.2 DNA Replication 12. The lagging strand must be replicated in discontinuous segments called Okazaki fragments. 13. Each segment of the lagging strand must begin with an RNA primer, then polymerase can add nucleotides in the 5′ to 3′ direction. (This is the direction of the new strand being formed.) 14. Then each RNA primer is removed and replaced with DNA. 15. The enzyme that covalently links the new segments of DNA after the RNA primer is removed is DNA ligase—forms phosphodiester bonds. Copyright © 2020 Nelson Education Ltd. 30 8.2 DNA Replication • Topoisomerase is an enzyme that is used to relieve supercoils in eukaryotic DNA as well as in prokaryotes that have circular DNA • In viruses, topoisomerase is used to integrate viral DNA into the genome of the cell it is infecting. Copyright © 2020 Nelson Education Ltd. 31 8.2 DNA Replication Copyright © 2020 Nelson Education Ltd. 32 Application Copyright © 2020 Nelson Education Ltd. 34 8.3 DNA Mutations • Because so much DNA is being replicated in the many cells of the body, there is potential for errors to occur. • We have about 130 genes that code for DNA repair enzymes. • Repair enzymes, as well as polymerase itself, compare the new DNA strand with the original DNA strand and fix any incorrect nucleotides. • This is called proofreading. • Proofreading is still not perfect and mistakes can occur—DNA mutations. • What happens if there are DNA mutations? Copyright © 2020 Nelson Education Ltd. 35 8.3 DNA Mutations • How do our cells deal with mutations? • Proofreading • Repairing enzymes • What if mutations still occur? • Apoptosis (programed cell death) • Immune cells that kill cancer cells • What if mutations still occur? • Disease Copyright © 2020 Nelson Education Ltd. 36 8.3 DNA Mutations There are two general ways to alter the genetic message encoded in DNA. • Point mutations • These result from errors in replication. • They can involve substitutions, additions, or deletions of nucleotides. • Recombination mutations • These cause a change in the position of all or part of a gene. Copyright © 2020 Nelson Education Ltd. 37 8.3 DNA Mutations • Approximately one in every 100 000 to 1 million base pairs will be a mismatch (substitution) during replication. • Generally, a mismatch causes polymerase to pause, and then the incorrect base pair enters the exonuclease section of the polymerase enzyme; this is proofreading. • Then the error can be removed and the correct nucleotides replace the mistake. Copyright © 2020 Nelson Education Ltd. 38 8.3 DNA Mutations • As well as polymerase, repair enzymes can also correct DNA mutations. • What are the consequences of DNA mutations • in a population of organisms? • in that specific organism? • What do you call a substance that mutates DNA? • Mutagen • What do you call a substance that mutates DNA and also causes cancer? • Carcinogen Copyright © 2020 Nelson Education Ltd. 39 8.3 DNA Mutations • Mutations can alter the genetic message and affect protein synthesis. • Most mutations occur randomly in a cell’s DNA, so most mutations are detrimental. • In what cell types can DNA mutations occur? • Mutations in germ cells • These mutations will be passed to future generations. • They are important for evolutionary change. • Mutations in somatic cells • These are not passed to future generations but are passed to all other somatic cells derived from them. Copyright © 2020 Nelson Education Ltd. 40 8.3 DNA Mutations Copyright © 2020 Nelson Education Ltd. 41 8.3 DNA Mutations • There are different types of DNA mutation. 1. Substitution changes the identity of a base or bases. 2. Insertion adds a base or bases. 3. Deletion removes a base of bases. • What would be the consequence of a deletion or addition? • A frame-shift mutation results. • These are extremely detrimental because the final protein intended by the message may be altered dramatically or it may not be made at all. Copyright © 2020 Nelson Education Ltd. 42 8.3 DNA Mutations THE CAT SAW THE DOG • Substitution • THE BAT SAW THE DOG • Insertion • THE CRA TSA WTH EDO G • Deletion • THE ATS AWT HED OG Copyright © 2020 Nelson Education Ltd. 43 8.3 DNA Mutations: Transposition • Transposable elements (TEs) are sequences of DNA that can move or transpose themselves within a cell. • The mechanism of transposition can be either “copy and paste” or “cut and paste.” • All living organisms contain transposable elements (also called transposons or jumping genes). • TEs play a significant role in phenotypic variation and evolution, but they can be detrimental to an organism. Copyright © 2020 Nelson Education Ltd. 44 8.3 DNA Mutations: Transposition • If a mutagen causes the sugar-phosphate backbone to break, the cell will try to repair this by adding the DNA fragment to another piece of DNA. • This can cause segments of DNA to be moved to entirely different chromosomes. • If this occurred in germ cells, how would this affect crossing over during meiosis? Copyright © 2020 Nelson Education Ltd. 45 8.3 DNA Mutations Copyright © 2020 Nelson Education Ltd. 46 8.3 DNA Mutations Copyright © 2020 Nelson Education Ltd. 47 8.3 DNA Mutations: Introns and Exons • Exons are the sequences in a gene that code for the mRNA that will code for the protein. • Introns are removed and do not become part of the RNA sequence. • Mutations in introns usually have no affect on the protein—silent mutations. • Also, some mutations occur in a base that does not affect the protein sequence. (This will be discussed later in more detail.) Copyright © 2020 Nelson Education Ltd. 48 8.3 DNA Mutations Natural killer cells can kill cancer cells. Copyright © 2020 Nelson Education Ltd. 49 8.3 DNA Mutations: Genetic Diseases • Cystic fibrosis: one mismatch base in the gene that codes for chloride channels • Huntington’s disease: insertion of multiple CAG repeats in a gene on chromosome 4 • Sickle cell anemia: one mismatch in the hemoglobin gene • Cancer: usually two or more mutations in genes that code for repair enzymes or in genes that affect the cell cycle. What are these called? • Oncogenes and tumour-suppressor genes Copyright © 2020 Nelson Education Ltd. 50 8.3 DNA Mutations: Genetic Diseases • Phenylketonuria (PKU): point mutation in liver enzyme gene, which causes brain damage. Babies are tested at birth for the presence of an enzyme that breaks down phenylalanine into tyrosine (amino acids). • Nonpolyposis colorectal cancer: autosomal, dominant, repeated CA mutation in DNA repair enzyme gene, a non-functional repair protein Copyright © 2020 Nelson Education Ltd. 51 How do we acquire DNA mutations? 1. 2. 3. 4. 5. Mistakes during DNA replication Transposition Inherited mutations (approximately 10% of all diseases) Mutagens and carcinogens (most common causes of mutation) Viruses Copyright © 2020 Nelson Education Ltd. 52 8.3 DNA Mutations: Mutagens • Radiation • UV light. This is the most common cause of skin cancers. • X-rays. Gamma radiation used for taking x-rays can cause multiple types of cancers. • Chemicals • Pesticides and herbicides • Industrial chemicals • Pollution, including cigarette smoke • Food additives and preservatives • Drugs Copyright © 2020 Nelson Education Ltd. 53 8.3 DNA Mutations: Mutagens Viruses • Human papilloma virus (HPV): genital warts that can cause cervical cancer • Human immunodeficiency virus (HIV): AIDS, which can cause Kaposi sarcoma and overgrowth of blood vessels • Hepatitis B or C: liver infection that can cause liver cancer • Epstein–Barr Virus (EBV): mononucleosis, which can cause lymphoma (rare) Copyright © 2020 Nelson Education Ltd. 54 Application Answer Copyright © 2020 Nelson Education Ltd. 55
