1 / 77

The “Central Dogma” Overview Of DNA How does DNA control the cell?

The “Central Dogma” Overview Of DNA How does DNA control the cell?. Transcription. Translation. DNA. mRNA. proteins. Enzymes Structure Movement Hormones Gas exchange Amino Acid Storage. Replication. So how does DNA “control” the cell?. Transcription. Translation. DNA. mRNA.

lilika
Download Presentation

The “Central Dogma” Overview Of DNA How does DNA control the cell?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. The “Central Dogma”Overview Of DNAHow does DNA control the cell? Transcription Translation DNA mRNA proteins Enzymes Structure Movement Hormones Gas exchange Amino Acid Storage Replication

  2. So how does DNA “control” the cell? Transcription Translation DNA mRNA proteins Enzymes Structure Movement Hormones Gas exchange Amino Acid Storage Replication

  3. Thomas Hunt Morgan

  4. Frederick Griffith

  5. Oswald Avery, Maclyn McCarty, and Colin MacLeod

  6. Alfred Hershey and Martha Chase

  7. Erwin Chargaff • A = 30.9% • T = 29.4% • G = 19.9% • C = 19.8%

  8. Watson, Crick, and Franklin

  9. Matthew Meselson and Franklin Stahl

  10. From DNA to Chromosome chromosome nucleus • A strand of human DNA is about 3 m long… • How does it fit into all our cells?? • Supercoiling cell Proteins that DNA wraps around histones Base pairs DNA

  11. Details of DNA Structure • Nucleotides are the monomers of nucleic acids • 5 carbon sugar • Ribose • Deoxyribose • Nitrogen Base • Adenine • Thymine • Cytosine • Guanine • Uracil • Phosphate 5’ Carbon 5’ 4’ 1’ 2’ 3’ 3’ Hydroxyl

  12. Details of DNA Structure 5’ Carbon 3’ Hydroxyl • What do you notice about the 5’ and 3’ ends of the two strands? • They’re ANTIPARALLEL!! • Why? For the nucleotide bases to line up 3’ Hydroxyl 5’ Carbon

  13. Details of DNA Structure 5’ Carbon 3’ Hydroxyl • What holds the nucleotides together? 3’ Hydroxyl 5’ Carbon

  14. Details of DNA Structure • Nucleotide Bases: Purines and Pyrimidines • PURINES • “Aggies are Pure” – A and G are Purines which have 2 rings • PYRIMIDINES • “TCU Cheerleaders build Pyramids” – T and C are Pyrimidines have one ring

  15. Key Questions • How do 3 m of DNA fit into each of our cells? (be specific!) • Why is a DNA molecule considered to have direction and to be “anti-parallel”? • What type of bonds form the sugar-phosphate backbone? • What type of bonds hold the nucleotide bases together? • From what you know about the bonding between base pairs, which pairs (A-T or G-C) do you think have more breaks and mistakes and why?

  16. Question: • How does the structure of DNA ensure the daughter strands will be identical to the parent strand?

  17. DNA Replication Parent strand Origin of replication Daughter strand Bubble Replication fork 2 new strands

  18. DNA Enzymes • Helicase • Breaks hydrogen bonds to unwind DNA • DNA Polymerase III • Adds nucleotides ONLY to the 3’ end • Nucleoside PPP links to sugar-P backbone • Losing 2 Ps provides energy for bonding

  19. Problem: Nucleotides can only be added to the 3’ end by DNA Polymerase… • Solution: Okazaki • Leading and Lagging Strands • Leading Strand • Continuous synthesis • Lagging Strand • Okazaki fragments • Joined by ligase

  20. 3’ Remember: DNA polymerase can only add nucleotides to the 3’ end, so DNA gets built in the 5’  3’ direction! 5’ Parental DNA 5’ Okazaki fragments 3’ DNA polymerase 3’ Ligase Leading and lagging have the same origin of replication, but since DNA polymerase can only add on the 3’ end, the lagging strand has to start backwards and make little pieces to link together 5’ Leading strand One piece of 5’  3’ Many little pieces of 5’  3’ linked together later Lagging strand

  21. Test your understanding…On some paper, write A – H and decide whether each letter represents the 3’ or 5’ end of DNA. Then, label the sections (A-B, C-D, etc) as “leading” or “lagging” A-B: Leading C-D: Lagging B C A D 5’ 3’ 3’ 5’ 3’ 5’ E H 3’ 5’ G F F-E: Leading H-G: Lagging

  22. Priming DNA Synthesis • DNA polymerase can only extend an existing DNA molecule; it cannot start a new one • Short RNA primer is built first on parent DNA by primase • RNA primer later removed by DNA polymerase I

  23. Priming DNA Synthesis • Closer look… Primase builds the RNA primer Replaces RNA nucleotides with DNA Primase DNA polymerase

  24. Putting it all together! • http://www.johnkyrk.com/DNAreplication.html

  25. Editing and Proofreading DNA Why do we not always get cancer? DNA can repair itself!!! • Since DNA polymerase III does 1,000 base pairs/second, it makes a lot of errors • DNA Polymerase I (only 20 bp/sec) excises mismatched bases, repairs the DNA, and removes the primer • DNA polymerase I reduces error from 1 in 10,000 bp to 1 in 100 million bp!!

  26. Problems at the end… • Ends of chromosomes are “eroded” with each replication (don’t get fully copied) • Telomeres are expendable, non-coding sequences at the ends of the DNA strand • short sequence of bases repeated 1000s of times • TTAGGG in humans

  27. Telomeres and Aging telomere • In the absence of telomerase, the telomere will become shorter after each cell division.  When it reaches a certain length, the cell may cease to divide and die.  telomerase Extended telomere

  28. Putting it ALL together • Summarize the roles of the key enzymes • Label the diagram showing the steps of DNA replication • DNA Structure – Questions and Practice

  29. Summary of Replication Enzymes Unzips DNA (breaks H-bonds between nucleotides) Builds RNA primer in leading strand and Okazaki fragments Adds DNA nucleotides (20 bp/s); replaces RNA primer with DNA; repairs errors in DNA Adds DNA nucleotides (1,000 bp/s) Joins Okazaki fragments (using phosphate groups)

  30. In the diagram below, label the key enzymes and structures in DNA replication. Be sure to label 3’ and 5’ ends, too!

  31. Protein Synthesis • How does DNA control the structure and function of the cell? it makes proteins! • Structure: collagen, elastin, keratin • Enzymes: catalase, amylase, sucrase, etc • Hormones: insulin, glucagon, etc • Amino acid storage: albumin, ovalbumin, etc

  32. The “Central Dogma”Overview Of DNA Transcription Translation DNA mRNA proteins Enzymes Structure Movement Hormones Gas exchange Amino Acid Storage Replication

  33. The “Main Things” forDNA Transcription and Translation

  34. Let’s model it…

  35. Protein Synthesis! • Transcription • http://www.johnkyrk.com/DNAtranscription.html • Translation • http://www.johnkyrk.com/DNAtranslation.html

  36. Notas – From Gene to Protein Metabolism teaches us about genes • Metabolic defects caused by non-functional enzyme • Studying metabolic diseases suggested that genes specified proteins • PKY • Alkaptonuria (black urine) • Genes dictate the phenotype

  37. 1 gene – 1 enzyme hypothesis • Beadle and Tatum – 1941

  38. 1 gene – 1 enzyme hypothesis • Beadle and Tatum – 1941 • Compared different nutritional mutants of bread mold, Neurospora • Created mutations by X-ray treatments X-rays break DNA) • Wild type grows on “minimal” media (sugar) • Mutants require different amino acids because each mutant lacks a certain enzyme needed to produce a certain amino acid • Conclusion: Broken gene = non-functional enzyme • Problems with: • One gene – one enzyme • not all proteins are enzymes, and they’re coded by genes too • One gene – one protein • many proteins consist of several polypeptide, and each polypeptide has it’s own gene • One gene – one polypeptide?

  39. Defining a gene… • “Defining a gene is problematic because small genes can be difficult to detect, one gene can code for several protein products, some genes code only for RNA, two genes can overlap, and there are many other complications.” – Elizabeth Pennisi, Science 2003 • How would YOU define a gene in your own words?

  40. The “Central Dogma” Transcription Translation DNA mRNA Protein Reverse Transcription Replication

  41. From nucleus to cytoplasm… • Where are the genes? in DNA on chromosomes in the nucleus • Where are proteins synthesized? on ribosomes (free or on the ER) in the cytoplasm • How does the information get from the nucleus to the cytoplasm? mRNA is made in the nucleus and can travel into the cytoplasm to the ribosomes

  42. deoxyribose ribose A-T, C-G T-A, A-U, C-G Double Single

  43. Transcription Basics • Initiation • RNA polymerase binds to promoter sequence on DNA • where to start reading = Promoter (initiation site) • which strand to read = template strand • direction on DNA = reads 3’5  builds 5’  3’ • Elongation • RNA polymerase unwinds DNA ~20 bp at a time • Reads DNA 3’  5’ • Builds RNA 5’  3’ • No proofreading, about 1 error/105 bases • Many copies, short life, no problem  • Termination • RNA polymerase stops at termination sequence • mRNA leaves nucleus through pores

  44. Transcription

  45. RNA Processing or Editing • 5’ cap • protection • targets mRNA for ribosome • Poly-A tail • protection • leads mRNA out of nucleus • Spliceosome • composed of snRNPs (small nuclear ribonucleoproteins) • introns – intervening, interrupting = removed by spliceosome • exons – expressed

  46. Sliceosome

  47. Putting it Together – Transcription to Translation • How does mRNA code for proteins? • How can you code for 20 aa with only 4 nucleotide bases (A, U, G, C)? • How can an alphabet of 4 letters (nucleotides) translate into an alphabet of 20 letters (aa)?!

  48. Breaking the code • Nirenberg and Matthaei • Determined 1st codon – amino acid match • UUU coded for phenylalanine • Created artificial poly(U) mRNA • Added mRNA to test tube of ribosomes and nucleotides • mRNA synthesized a single amino acid polypeptide chain: phe-phe-phe-phe-phe-phe

More Related