The DNA Molecule: The Molecular Basis of Inheritance

Transcription

1 Slide hapter 6 he DN Molecule: he Molecular Basis of Inheritance PowerPoint Lecture Presentations for Biology Eighth Edition Neil ampbell and Jane Reece Lectures by hris Romero, updated by Erin Barley with contributions from Joan Sharp opyright 008 Pearson Education, Inc., publishing as Pearson Benjamin ummings Slide he Structure of Nucleic cids What are the nucleic acids monomers called? What are the nucleic acid polymers called? opyright 008 Pearson Education, Inc., publishing as Pearson Benjamin ummings Slide 3 Fig. 5-7 end Each nucleotide consists of a nitrogenous base, a pentose sugar, and a phosphate group Nitrogenous bases Pyrimidines Nucleoside Nitrogenous base ytosine () hymine (, in DN) Uracil (U, in RN) Purines Phosphate group Sugar (pentose) denine () uanine () end Polynucleotide, or nucleic acid Deoxyribose (in DN) Sugars Ribose (in RN) he nucleotide without the phosphate is called a nucleoside

2 Slide 4 Fig. 5-UN6 ovalent bonds formed between the OH group on the carbon of one nucleotide and the phosphate on the carbon on the next he sequence of bases along a DN or mrn polymer is unique for each gene Backbone of sugarphosphate units with nitrogenous bases as appendages One DN molecule includes many genes! Slide 5 Fig. 5-8 wo polynucleotides spiraling around an imaginary axis form a Double Helix 5' end 3' end Sugar-phosphate backbones Base pair (joined by hydrogen bonding) Old strands What is meant by ntiparallel? 3' end Nucleotide about to be added to a new strand 5' end 3' end New strands 5' end 5' end 3' end Slide 6 Fig. 6-7 end nm 3.4 nm Hydrogen bond end end 0.34 nm end Would you suspect the nitrogenous bases to be hydrophilic or hydrophobic?

3 Slide 7 What DN bases can pair up? and and How many DN molecules do we have? How many do bacteria have? Slide 8 Fig. 6-8 denine () hymine () uanine () ytosine () Slide 9 953: Watson and rick Publish the Structure of DN "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."watson and rick One-page paper in the journal, Nature - Structure of DN suggests its function (DN replication)

4 Slide 0 Fig. 6-6 Maurice Wilkins and Rosalin Franklin were using X-ray crystallography to study molecular structure of DN (a) Rosalind Franklin (b) Franklin s X-ray diffraction photograph of DN Slide Fig. 6-0 Which model is correct? Parent cell First replication Second replication (a) onservative model (b) Semiconservative model (c) Dispersive model Slide Fig (a) Parent molecule (b) Separation of strands (c) Daughter DN molecules, each consisting of one parental strand and one new strand Since the two strands of DN are complementary, each strand acts as a template for building a new strand in replication In DN replication, the parent molecule unwinds, and two new daughterstrands are built based on base-pairing rules

5 Slide 3 DN Replication: loser Look he copying of DN is remarkable in its speed and accuracy More than a dozen enzymes and other proteins participate in DN replication opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 4 etting Started Replication begins at special sites called origins of replication, where the two DN strands are separated, opening up a replication bubble eukaryotic chromosome may have hundreds or even thousands of origins of replication Replication proceeds in both directions from each origin, until the entire molecule is copied opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings nimation: Origins of Replication Slide 5 Fig. 6-a Origin of replication Doublestranded DN molecule wo daughter DN molecules Single origin of replication in E. coli Parental (template) strand Daughter (new) strand Replication bubble Replication fork Many bacteria have a single, circular chromosomes with one origin of replication 0.5 µm

6 Slide 6 Fig. 6-b Multiple origins of replication in eukaryotes Origin of replication Double-stranded DN molecule Parental (template) strand Daughter (new) strand 0.5 µm Bubble Replication fork wo daughter DN molecules Slide 7 Fig. 6-5a Overview: Different hings oing On. Leading strand synthesis. Lagging strand synthesis Origin of replication Leading strand Lagging strand Primer Lagging strand Replication forks move in opposite directions Leading strand Slide 8 Leading Strand Synthesis DN polymerases add nucleotides only to the free end of a growing strand; therefore, a new DN strand can elongate only in the to direction long one template strand of DN, the DN polymerase synthesizes a leading strand continuously, moving toward the replication fork opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings

7 Slide 9 Fig. 6-3 Replication Fork Single-strand binding proteins Primase opoisomerase RN primer Helicase What function do each of these enzymes perform? Slide 0 DN polymerases can t initiate synthesis of a polynucleotide; they can only add nucleotides to the end he initial nucleotide strand is a short RN primer n enzyme called primase can start an RN chain from scratch and adds RN nucleotides one at a time using the parental DN as a template he primer is short (5 0 nucleotides long), and the end serves as the starting point for the new DN strand Slide Fig. 6-5b Origin of replication Parental DN RN primer Sliding clamp DN pol III

8 Slide Each nucleotide that is added to a growing DN strand is a nucleoside triphosphate dp supplies adenine to DN and is similar to the P of energy metabolism he difference is in their sugars: dp has deoxyribose while P has ribose s each monomer of dp joins the DN strand, it loses two phosphate groups as a molecule of pyrophosphate opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 3 Fig. 6-4 New strand end emplate strand end end end Sugar Phosphate Base end DN polymerase Nucleoside triphosphate end Pyrophosphate end end Slide 4 Lagging Strand Synthesis o elongate the other new strand, called the lagging strand, DN polymerase must work in the direction away from the replication fork he lagging strand is synthesized as a series of segments called Okazaki fragments, which are joined together by DN ligase opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings

9 Slide 5 Fig. 6-6a Overview Origin of replication Leading strand Lagging strand Lagging strand Overall directions of replication Leading strand Slide 6 Fig. 6-6b Enzyme? emplate strand Slide 7 Fig. 6-6b emplate strand Enzyme? RN primer

10 Slide 8 Fig. 6-6b3 emplate strand RN primer Okazaki fragment Slide 9 Fig. 6-6b4 emplate strand RN primer Okazaki fragment Slide 30 Fig. 6-6b5 emplate strand RN primer Okazaki fragment Enzyme?

11 Slide 3 Fig. 6-6b6 emplate strand RN primer Okazaki fragment Enzyme? Overall direction of replication Slide 3 able 6- Slide 33 Fig. 6-7 Describe this figure What is each enzyme doing? Single-strand binding protein Overview Origin of replication Leading strand Lagging strand Leading strand Lagging strand Overall directions of replication Helicase Parental DN DN pol III Primer Primase Leading strand DN pol III Lagging strand DN pol I 4 3 DN ligase

12 Slide 34 he DN Replication omplex he proteins that participate in DN replication form a large complex, a DN replication machine he DN replication machine is probably stationary during the replication process Recent studies support a model in which DN polymerase molecules reel in parental DN and extrude newly made daughter DN molecules opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings nimation: DN Replication Review Slide 35 Proofreading and Repairing DN Replication has an error rate at ~ in 00,000 nucleotides, but DN polymerases proofread newly made DN, replacing any incorrect nucleotides (only in 0 billion errors occur following this process). In mismatch repair of DN, repair enzymes correct errors in base pairing (usually just after replication) DN can also be damaged by chemicals, radioactive emissions, X-rays, UV light, and certain molecules (in cigarette smoke for example) In nucleotide excision repair, a nuclease cuts out and replaces damaged stretches of DN opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 36 Fig. 6-8 hymine Dimer What is a thymine dimer? Describe the Steps in Nucleotide Excision Repair Nuclease DN polymerase DN ligase

13 Slide 37 Replicating the Ends of DN Molecules Limitations of DN polymerase create problems for the linear DN of eukaryotic chromosomes he usual replication machinery provides no way to complete the ends of daughter DN strands, so repeated rounds of replication produce shorter DN molecules opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 38 Fig. 6-9 Ends of parental DN strands Describe the shortening of linear DN molecules with each round of replication. Lagging strand Parental strand Last fragment RN primer Leading strand Lagging strand Previous fragment Removal of primers and replacement with DN where a end is available Second round of replication New leading strand New lagging strand Further rounds of replication Shorter and shorter daughter molecules Slide 39 Fig. 6-0 Eukaryotic chromosomal DN molecules have at their ends nucleotide sequences called telomeres (stained dots above) elomeres do not prevent the shortening of DN molecules, but they do postpone the erosion of genes near the ends of DN molecules It has been proposed that the shortening of telomeres is connected to aging

14 Slide 40 If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce n enzyme called telomerase catalyzes the lengthening of telomeres in germ cells he shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions here is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 4 oncept 6.3 chromosome consists of a DN molecule packed together with proteins In Bacteria: he chromosome is a double-stranded, circular DN molecule associated with a small amount of protein the DN is supercoiled and found in a region of the cell called the nucleoid In Eukaryotes: chromosomes have linear DN molecules associated with a large amount of protein hromatin is a complex of DN and protein found in the nucleus of eukaryotic cells Histones are proteins that are responsible for the first level of DN packing in chromatin opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 4 Fig. 6-a DN double helix ( nm in diameter) Histones Nucleosome (0 nm in diameter) Histone tail DN, the double helix Histones Nucleosomes, or beads on a string (0-nm fiber) H

15 Slide 43 Fig. 6-b hromatid (700 nm) 30-nm fiber Loops Scaffold 300-nm fiber 30-nm fiber Looped domains (300-nm fiber) Replicated chromosome (,400 nm) Metaphase chromosome Slide 44 hromatin is organized (packed) into fibers 0-nm fiber: DN winds around histones to form nucleosome beads Nucleosomes are strung together like beads on a string by linker DN 30-nm fiber Interactions between nucleosomes cause the thin fiber to coil or fold into this thicker fiber 300-nm fiber he 30-nm fiber forms looped domains that attach to proteins Metaphase chromosome he looped domains coil further he width of a chromatid is 700 nm opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 45 hromatin undergoes changes in its degree of packing during the cell cycle it is dynamic Most chromatin is loosely packed in the nucleus but condenses prior to cell division Loosely packed chromatin is called euchromatin Heterochromatin, or highly condensed chromatin is inaccessible to gene expression machinery Histones can undergo chemical modifications that result in changes in chromatin organization For example, phosphorylation of a specific amino acid on a histone tail affects chromosomal behavior during meiosis opyright 008 Pearson Education Inc., publishing as Pearson Benjamin ummings