DNA Structure & Chromosome Organisation Module 2022-2023 PDF

DUHOK Medical College 2022– 2023 Professor. Dr.Asaad,A.B.Alasady 1 • Human Heredity Chapter 8 • Marks’ Basic Medical Biochemistry Chapters 12, 13 • Medical Biochemistry Chapters 31 • Lippincott’s Illustrated Reviews: Biochemistry Chapters 29 2 3 At the end of this Lecture you should be able...

DUHOK Medical College 2022– 2023 Professor. Dr.Asaad,A.B.Alasady 1 • Human Heredity Chapter 8 • Marks’ Basic Medical Biochemistry Chapters 12, 13 • Medical Biochemistry Chapters 31 • Lippincott’s Illustrated Reviews: Biochemistry Chapters 29 2 3 At the end of this Lecture you should be able to: 1) Recognize the structural components of a DNA and a RNA molecule. (LO 4.1) 2) Recognize and apply the conventions used to represent these components and the conventions used to represent DNA or RNA base sequences. (LO 4.2) 3) Explain polarity of a DNA or RNA chain. (LO 4.3) 4)Explain the importance of hydrogen-bonding and base-pairing in defining nucleic acid secondary structure. (LO 4.4) 5)Describe the key features of the DNA double helix. (LO 4.5) 4 The Central Dogma of Molecular biology The Central Dogma: is The flow information from DNA to RNA to Protein in all organism. § In most of organism the DNA is storage the genetic information with exception of some viruses have RNA as the repository of their genetic information. 5 Gene: Basic unit of biological information; specific segments of DNA composed of distinctive sets of nucleotide pairs in a discrete region of a chromosome that encodes a particular protein; a coding locus Genotype: The genetic composition of an individual, especially in terms of the alleles for particular genes(i.e. Aa or aa) Alleles: Alternative forms of a single gene • One pair of Homologous Chromosomes: Gene for eye color (blue eyes) Homologous pair of chromosomes Gene for eye color (brown eyes) Phenotype: Characteristic of an individual observed or discernible by other means (i.e. color blindness or blood type in humans). colorblindness – inability to distinguish between certain colors You should see 58 (upper left), 18 (upper right), E (lower left) and 17 (lower right). Color blindness is the inability to distinguish the differences between certain colors. The most common type is red-green color blindness, where red and green are seen as the same color. Nucleic Acids: DNA and RNA Nucleic Acids: Are linear polymers of nucleotides ‘polynucleotides’ that required for the storage and expression of genetic information. There are two chemically distinct types of nucleic acids: v Deoxyribonucleic acid (DNA): Is polymer of deoxyribonucleotides covalently linked by 3‫׳‬5→‫ ׳‬phosphodiester bond carrying the genetic information in all cellular forms of life and some viruses. v Ribonucleic acid (RNA): Is polymer of ribonucleotides covalently linked by 3‫׳‬5→‫ ׳‬phosphodiester bond that function as an intermediary in the transfer of genetic information from DNA to protein. carrying the genetic information in RNA viruses 6 Nucleotides: Building blocks of nucleic acids LO 4.1) Nucleotides : are basic building block of DNA and RNA Each nucleotide consists of three components: Nitrogenous base Pentose sugar Phosphate molecule While nucleoside composed of only : Nitrogenous base and Pentose sugar Nucleotides: Building blocks of nucleic acids Nucleotides Components Ø Nitrogenous base: there are two types üThere is similarity between the 6-membered rings üThese structures are ‘planar’ (it can be represented on a flat surface) because of the double bonds, and unsaturated MGD 2021 /2022 8 Nucleotides: Building blocks of nucleic acids Nucleotides Components Ø Nitrogenous base: there are two types 1-Purine: have a two-ring structure [Adenine (A) and Guanine (G)] 2-Pyrimidine: have a one-ring structure [Thymine (T) Cytosine (C) and Uracil (U)] MGD 2022 /2023 Dr. Asaad ,A.B.Alasady DNA has A,G,T,C and RNA has A,G,U,C 9 Nucleotides: Building blocks of nucleic acids Nucleotides Components Ø Pentose sugar: there are two types Ø Phosphate group: The phosphate groups are strongly acidic and are the reason DNA and RNA are called acids. MGD 2022 /2023 DR. Asaad,A.B.Alasady OH HO P O O 10 Nucleotides: Building blocks of nucleic acids Nucleotides Structure Nucleotides: are formed by covalent bonding of the phosphate, base, and sugar. MGD 2022 /2023 DR. Asaad,A,B.Alasady 11 Nucleotides: Building blocks of nucleic acids (LO 4.2) 12 Nucleotides: Building blocks of nucleic acids 13 Nucleotides: Building blocks of nucleic acids (LO 4.3) Polynucleotides: Formation and Characteristics ØNucleotides are covalently linked via 3'→5' phosphodiester bonds to form polynucleotides chains. ØThe resulting chain has polarity, with both a 5'end (the end with free phosphate) and a 3'-end ( the end with free hydroxyl group) that are not linked to other nucleotides, resulting in Chain with 5'→3' direction Ø The bases written in the conventional 5'→3' direction: 5'-AGCT-3‘ Ø DNA has two polynucleotides chains and RNA has only one Ø Each single-strand nucleic acid chain has a polarity 3 5 OH P HO HN O NH N O N CH2 O HO P O N OH H H2 O N O NH2 N O 2 N N CH2 H O O OH O N H P HO H N N O O O CH2 O N O O O N H2 H N CH2 H P HO OH O 3’Hydroxyl group H2 O N O NE CH2 N HN N 5’Phosphate group HO O O O H P NH2 HO P O H O HO O HATE BACKBO D N A N O CH2 O NH2 O 3’Hydroxyl group 3 CH S B A S E SUGAR-PHOSP 5’Phosphate group Deoxyribonucleic acid (DNA) (LO 4.4) Key features of DNA: Watson-Crick Model of DNA Structure According to Watson and Crick model (1953), DNA characterizes by: DNA is composed of two polynucleotide chains running in opposite directions, one chain run in direction, the other in direction. Ø : is highly specific: Adenine( A) in one chain pairs with Thymine(T) in the opposite chain by two hydrogen bonds, and C pairs with G by three hydrogen bonds. 15 The hydrogen bonds forms between (A & T) or between (G & C) Why????? Base pairing Base-pairing in DNA A with T and G with C ,based on hydrogen-bonding between appropriately spaced negatively charged =O and N groups and positively charged H’s. Note that the similar opposition of adenine and cytosine or G and T results in the juxtaposition of identically charged(+ or -) groups at two of the three sites of potential hydrogen bonding. Thus, A is not normally found base-paired with C,nor G with T in DNA. Base Pairing Guanine And Cytosine O N H + N H - N H - e H + osin C yt N N H N ne a ni Gu + - N N O Base Pairing CH N N + Thymine O N N - N H O N Adenine N + H H 3 Adenine And Thymine Base Pairing Adenine And Cytosine N N N N N H - - e denine AN H + + H osin Cyt H N N O Base Pairing - O H + + e n i m y h T N N - O H N N H N ne a ni Gu O N CH 3 Guanine And Thymine N H + (LO 4.5) Deoxyribonucleic acid (DNA) According to Watson and Crick model (1953), DNA characterizes by: Ø The base pairing of the model makes the two polynucleotide chains of DNA complementary in base composition. If one strand has the sequence the opposite strand must be and the double-stranded structure would be written as: Ø Chargaff Rule (base ratio): Ø Ø _ _ 16 Chargaff Rule (base ratio): State that DNA from any cell of any organisms should have a 1:1 ratio (base Pair Rule) of pyrimidine and purine bases and, more specifically, that the amount of guanine should be equal to cytosine and the amount of adenine should be equal to thymine. This pattern is found in both strands of the DNA. Deoxyribonucleic acid (DNA) 17 Deoxyribonucleic acid (DNA) Ø The two chains are twisted (coiled) around each other in a right-handed to form a double helix ( ). § The hydrophilic deoxyribose-phosphate backbone of each chain is on the outside the molecule § Whereas the hydrophobic bases are stacked inside where they are paired by hydrogen bonds. The overall structure resembles the twisted ladder. § One complete turn is 10 base pairs and space between base pairs is 0.34nm. § The spatial relationship between the two strands in the helix creates a major (wide) groove and a minor (narrow) groove. The bases in these grooves exposed and therefore interact with proteins or other molecules. 18 Deoxyribonucleic acid (DNA) Ø Negative charge: The third -OH group on the phosphate is free and dissociates a hydrogen ion at physiologic pH. Therefore, each DNA helix has negative charges coating its surface that facilitate the binding of specific proteins. 19 Deoxyribonucleic acid (DNA) vGenetic information is stored in the sequence of bases in the DNA, which have a high coding capacity . vThe model offers a molecular explanation for mutation. Because genetic information is stored as a linear sequence of bases in DNA, any change in the order or number of bases in a gene can result in a mutation that produces an altered phenotype v The complementary nature of the two polynucleotide DNA strands helps explain how DNA is copied; each strand can be used as a template to reconstruct the base sequence in the opposite strand, and also the mechanisms of transcription and translation (allows a strand of DNA to serve as a template for the synthesis of a complementary strand of RNA that used to direct the process of protein synthesis). 20 Deoxyribonucleic acid (DNA) Ø : The double strands can separate into single strands by disruption the hydrogen bonds between the paired bases using acidic or alkaline pH or heating. (phosphodiester bond are not broken by such treatment). Ø Complementary DNA strands can reform the double helix under appropriate conditions. Ø DNA degradation: Phosphodiester bonds (in DNA & RNA) can be cleaved hydrolytically by chemicals, or hydrolyzed enzymatically by nucleases (deoxyribonucleases), only RNA can be cleaved by alkali 1 21 Structural forms DNA double helix There are three major structural forms of DNA that all exhibit Watson and Crick complementary base pairing and antiparallel: A, B and Z forms: B form: is the chief form in the cells, is a right handed double helix with 10 base pair (bp) per turn of helix. A form: is produced form moderately dehydrating B form, is a right handed double helix with 11 base pair (bp) per turn Z-form: is zigzag structure, a left handed with 12 base pair (bp) per turn, which may occur naturally in stretches of DNA that contain alternating purine and pyrimidine ( ex. Poly GC),. Transition between B an2d2 z forms may play a role in regulating gene expression. Ribonucleic acid (RNA) vRNA: is polymer of ribonucleotides covalently linked by 3'→5' phosphodiester bonds. v RNA: is single strand that has direction from 5'→3' and Bases sequence always written from 5'-end to 3'-end: 5'- AGCU-3' v Phosphodiester bonds: can be cleaved hydrolytically by chemicals, or hydrolyzed Enzymatically by nucleases (ribonucleases). vRNA Formation and its role: will be discussed in details in lecture 9. 23