MgD S4 Lecture 1: DNA Structure and Chromosome Organization PDF

DNA Structure and Chromosome Organization Phosphate group: The phosphate groups are strongly Nucleic Acids: DNA and RNA Nucleic Acids: Are linear polymers of nucleotides ‘polynucleotides’ that required for the storage and expression of genetic information. acidic and are the reason DNA and RNA are...

DNA Structure and Chromosome Organization Phosphate group: The phosphate groups are strongly Nucleic Acids: DNA and RNA Nucleic Acids: Are linear polymers of nucleotides ‘polynucleotides’ that required for the storage and expression of genetic information. acidic and are the reason DNA and RNA are called acids. It attaches to pentose sugar by Phosphate ester bond. The base sequence of a nucleic acid strand is written by convention, in the 5' to 3' direction (left to right). -There are two chemically distinct types of nucleic acids: •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. •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 DNA RNA GTAC GUAC Nucleotides: are basic building block of DNA and RNA . formed by covalent bonding of the phosphate, base, and sugar. consist of three components: Nitrogenous base: a component of a nucleic acid Pentose sugar: There are two types •Pyrimidine: have a one-ring structure (Cytosine C, Uracil U & Thymine T,). •Larger name (10 letters), smaller structure (one ring). • Cytosine, Uracil & Thymine (CUT). • Cytosine & thymine are found in DNA while uracil in RNA. According to this convention, the sequence of the bottom strand in the Figure bellow must be written as: 5’ AGTACG 3’ or AGTACG. If written backward, the ends must be labeled: 3'- TCATGC -5' • Ribose • Found in RNA. •Contains OH group in carbon number 2. • Deoxyribose • Found in DNA. • Absence of OH in carbon 2. polarity of a DNA or RNA chain Each single-stranded nucleic acid chain has a polarity, two distinct ends: •5’ end with a free phosphate •3’end with a free OH-group. While nucleoside composed of only: • Nitrogenous base • Pentose sugar involved in base pairing, i.e. Guanine (G), Adenine (A), Thymine (T), Cytosine (C) and Uracil (U). It attaches to pentose sugar by N- glycocidic bond. There are two types of nitrogenous bases: •Purine: have a two-ring structure (Adenine A & Guanine G) • Smaller name (6 letters), larger structure (2 rings). • Pure As Gold. • Found in DNA & RNA. Representation of nucleic acids base sequences: Nucleotides Nomenclature: •Nucleotides are covalently linked via 3'→5' phosphodiester bonds to form polynucleotides chains. •The 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. •DNA has two polynucleotides chains and RNA has only one & each single-strand nucleic acid chain has a polarity the importance of hydrogen-bonding and basepairing in defining nucleic acid secondary structure. Base pair (bp): In double stranded nucleic acids a pair of nitrogenous bases held together by hydrogen bonds. It is always formed by one purine and one pyrimidine. • G always pairs up with C and stabilized by 3 hydrogen bonds. • A pairs up with T (in DNA) or with U (in RNA) and stabilized by 2 hydrogen bonds. -As a consequence of base pairing, the two strands of DNA are complementary; that is, adenine on one strand corresponds to thymine on the other strand, and guanine corresponds to cytosine. •Although the hydrogen bonds hold the bases and thus the two DNA strands together, they are weaker than covalent bonds and allow the DNA strands to separate during replication and transcription. the key features of the DNA double helix. According to Watson and Crick model (1953), DNA characterizes by: • (Antiparallel) DNA is composed of two polynucleotide chains running in opposite directions (antiparallel), one chain run in 5'→3'direction, the other in 3'→5'direction. • (Base pairing) is highly specific: A in one chain pairs with T in the opposite chain by two hydrogen bonds, and C pairs with G by three bonds. • (complementary)The base pairing of the model makes the two polynucleotide chains of DNA complementary in base composition. If one strand has the sequence 5′-ACGTC-3′, the opposite strand must be 3′-TGCAG-5. • 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. A=T, G = C, Total purines=Total pyrimidines The hydrogen bonds forms between (A & T) or between (G & C) Why?? •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. •The two chains are twisted (coiled) around each other in a right-handed to form a double helix (secondary structure) “ B form” DNA structure •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. • 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. three important properties of the Watson Crick Model: Summary 1. Genetic information is stored in the sequence of bases in the DNA, which have a high coding capacity. A DNA molecule n base pairs long has 4n combinations. That means that a sequence of 10 nucleotides has 410, or 1,048,576, possible combinations of nucleotides. 2. The 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. 3. 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). DNA Denaturation, Renaturation & Degradation: DNA Denaturation & Renaturation: the double strands can separate into single strands by disruption the hydrogen bonds between the paired bases using acidic, alkaline pH or heating. (Phosphodiester bond are not broken by such treatment). Complementary DNA strands can reform the double helix under appropriate conditions. 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. Hemi1n