Molecular Basis of Inheritance 2024/2025 PDF

First Semester 2024/2025 Presenter: Dr. Ibrahim Sale Weeks Number: 11-12 © 2021 Pearson Education Ltd.  DNA Is the Genetic Material DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group The nitrogenous bases can be adenine...

First Semester 2024/2025 Presenter: Dr. Ibrahim Sale Weeks Number: 11-12 © 2021 Pearson Education Ltd.  DNA Is the Genetic Material DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group The nitrogenous bases can be adenine (A), thymine (T), guanine (G), or cytosine (C) In 1950, Erwin Chargaff reported that DNA composition varies from one species to the next This evidence of molecular diversity among organisms made DNA a more credible candidate for the genetic material © 2021 Pearson Education Ltd.  Two findings became known as Chargaff’s rules – The base composition of DNA varies between species – In any species the number of A and T bases is equal and the number of G and C bases is equal The basis for these rules was not understood until the discovery of the double helix © 2021 Pearson Education Ltd. Figure 16.5 © 2021 Pearson Education Ltd. Building a Structural Model of DNA After DNA was accepted as the genetic material, the challenge was to determine how its structure accounts for its role in inheritance Maurice Wilkins and Rosalind Franklin used a technique called X-ray crystallography to study molecular structure Franklin produced a picture of the DNA molecule using this technique © 2021 Pearson Education Ltd. © 2021 Pearson Education Ltd.  Franklin’s X-ray crystallographic images of DNA allowed James Watson to deduce that DNA was helical The X-ray images also enabled Watson to deduce the width of the helix and the spacing of the nitrogenous bases The pattern in the photo suggested that the DNA molecule was made up of two strands, forming a double helix © 2021 Pearson Education Ltd.  Watson and Crick built models of a double helix to conform to the X-rays and chemistry of DNA Franklin had concluded that there were two outer sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior Watson built a model in which the backbones were antiparallel (their subunits run in opposite directions) © 2021 Pearson Education Ltd. Figure 16.7 © 2021 Pearson Education Ltd.  At first, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width Instead, pairing a purine (A or G) with a pyrimidine (C or T) resulted in a uniform width consistent with the X-ray data © 2021 Pearson Education Ltd. Figure 16.8 © 2021 Pearson Education Ltd.  Watson and Crick reasoned that the pairing was more specific, dictated by the base structures They determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C) The Watson-Crick model explains Chargaff’s rules: in any organism the amount of A = T, and the amount of G = C © 2021 Pearson Education Ltd. Figure 16.9 © 2021 Pearson Education Ltd.  DNA REPLICATION The copying of DNA is called DNA replication © 2021 Pearson Education Ltd. The Basic Principle: Base Pairing to a Template Strand Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication This yields two exact replicas of the “parental” molecule © 2021 Pearson Education Ltd.  Watson and Crick’s semiconservative model of replication predicts that when a double helix replicates, each daughter molecule will have one old strand (derived or “conserved” from the parent molecule) and one newly made strand Competing models were the conservative model (the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new) © 2021 Pearson Education Ltd. Figure 16.11 © 2021 Pearson Education Ltd. DNA Replication: A Closer Look The copying of DNA is remarkable in its speed and accuracy More than a dozen enzymes and other proteins participate in DNA replication Replication in bacteria is best understood, but evidence suggests that the replication process in eukaryotes and prokaryotes is fundamentally similar © 2021 Pearson Education Ltd.  Initiation of DNA replications Replication begins at particular sites called origins of replication, where the two DNA strands are separated, opening up a replication “bubble” A 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 © 2021 Pearson Education Ltd. Figure 16.13 © 2021 Pearson Education Ltd.  At the end of each replication bubble is a replication fork, a Y-shaped region where parental DNA strands are being unwound Helicases are enzymes that untwist the double helix at the replication forks Single-strand binding proteins bind to and stabilize single-stranded DNA Topoisomerase relieves the strain of twisting of the double helix by breaking, swiveling, and rejoining DNA strands © 2021 Pearson Education Ltd. Figure 16.14 © 2021 Pearson Education Ltd. Synthesizing a New DN A Strand DNA polymerases require a primer to which they can add nucleotides The initial nucleotide chain is a short R N A primer This is synthesized by the enzyme primase The completed primer is five to ten nucleotides long The new D N A strand will start from the 3′ end of the R N A primer © 2021 Pearson Education Ltd.  Enzymes called DNA polymerases catalyze the synthesis of new DNA at a replication fork Most DNA polymerases require a primer and a DNA template strand The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells © 2021 Pearson Education Ltd.  Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate dATP supplies adenine to DNA and is similar to the ATP of energy metabolism The difference is in their sugars: dATP has deoxyribose while ATP has ribose As each monomer joins the DNA strand, via a dehydration reaction, it loses two phosphate groups as a molecule of pyrophosphate © 2021 Pearson Education Ltd. Figure 16.15 © 2021 Pearson Education Ltd. Antiparallel Elongation The antiparallel structure of the double helix affects replication DNA polymerases add nucleotides only to the free 3′ end of a growing strand; therefore, a new DNA strand can elongate only in the 5′ → 3′ direction Along one template strand of DNA, the DNA polymerase synthesizes a leading strand continuously, moving toward the replication fork To elongate the other new strand, called the lagging strand, DNA polymerase must work in the direction away from the replication fork The lagging strand is synthesized as a series of segments called Okazaki fragments, which are joined together by DNA ligase © 2021 Pearson Education Ltd. Figure 16.16 © 2021 Pearson Education Ltd. Figure 16.17 © 2021 Pearson Education Ltd. Figure 16.18 © 2021 Pearson Education Ltd. © 2021 Pearson Education Ltd. The DNA Replication Complex The proteins that participate in DNA replication form a large complex, a “DNA replication machine” The DNA replication machine may be stationary during the replication process Recent studies support a model in which DNA polymerase molecules “reel in” parental DNA and extrude newly made daughter DNA molecules The exact mechanism is not yet resolved © 2021 Pearson Education Ltd. Figure 16.19 © 2021 Pearson Education Ltd. Proofreading and Repairing DNA DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides In mismatch repair of DNA, repair enzymes replace incorrectly paired nucleotides that have evaded the proofreading process © 2021 Pearson Education Ltd.  DNA can be damaged by exposure to harmful chemical or physical agents such as cigarette smoke and X-rays; it can also undergo spontaneous changes In nucleotide excision repair, a nuclease cuts out and replaces damaged stretches of DNA © 2021 Pearson Education Ltd. Figure 16.20 © 2021 Pearson Education Ltd.  Summary of key concepts: many proteins work together in DNA replication and repair © 2021 Pearson Education Ltd.