Biochemical Organization &Functions of DNA Lecture # 4 Dr. Shumaila Asim

Learning Outcomes Knowledge; Describe the biochemical Organization & Functions of DNA Describe the three-dimensional structure of DNA. Discuss the flow of genetic information (from DNA to RNA to protein) Content Biochemical Organization of DNA Functions of DNA

DNA stands for deoxyribose nucleic acid This chemical substance is present in the nucleus of all cells in all living organisms DNA controls all the chemical changes which take place in cells The kind of cell which is formed, (muscle, blood , nerve etc) is controlled by DNA The kind of organism which is produced (buttercup,giraffe,, human etc) is controlled by DNA

Structure and function of DNA Primary structure Definition: the base sequence (or the nucleotide sequence) in poly deoxynucleotide chain. The smallest DNA in nature is virus DNA. The length of 174 virus DNA is 5,386 bases (a single chain). The DNA length of human genome is 3,000,000,000 pair bases.

3’,5’ phosphodiester bond link nucleotides 5’end Phosphodiester bond 3’ end: free hydroxyl (-OH) group 3’,5’ phosphodiester bond link nucleotides together to form polynucleotide chains

The structure of a DNA chain can be concisely represented An even more abbreviated notation for this chain is pApCpGpTpA pACGTA The base chain is written in the 5’ →3’ direction

Secondary structure The secondary structure is defined as the relative spatial position of all the atoms of nucleotide residues.

— DNA double helix structure Secondary structure — DNA double helix structure Francis H.C. Crick Watson and Crick , 1953 The genetic material of all organisms except for some viruses. The foundation of the molecular biology. James D. Watson

The discovery of DNA double helix Chargaff's Rule (A=T, G=C in DNA) Franklin, Wilkins: X-ray Diffraction Refined Structure

DNA double helix Essential for replicating DNA and transcribing RNA Two separate strands Antiparellel (5’3’ direction) Base pairing: hydrogen bonding that holds two strands together Complementary (sequence) 3’ 5’ Sugar-phosphate backbones (negatively charged): outside Base pairs (stack one above the other): inside 3’ 5’

4 1 3 2 7 6 8 5 1 9 4 2 3 A:T G:C Base pairing

B form of DNA double helix Right-handed helix; The diameter of the double helix：2 nm The distance between two base pairs: 0.34 nm; Each turn of the helix involves 10 bases pairs, 3.4 nm. Stable configuration can be maintained by hydrogen bond and base stacking force (hydrophobic interaction).

Major & Minor Grooves in a space-filling model of DNA The major and minor grooves are opposite each other, and each runs continuously along the entire length of the DNA molecule. They arise from the antiparallel arrangement of the two backbone strands. Note that the grooves are actual structural features of the molecule, not consequences of the way it is drawn. The grooves are important in the attachment of DNA Binding Proteins involved in replication and trascription.

Groove binding Small molecules like drugs bind in the minor groove, whereas particular protein motifs can interact with the major grooves.

Watson, Crick, and Wilkins shared the Nobel Prize in 1962 for this brilliant accomplishment. The discovery of the DNA double helix revolutionized biology: it led the way to an understanding of gene function in molecular terms (their work is recognized to mark the beginning of molecular biology).

Conformational variation in double-helical structure B-DNA A-DNA Z-DNA

It is the standard structure for DNA molecules. B-form: the duplex structure proposed by Watson and Crick is referred as the B-form DNA. It is the standard structure for DNA molecules. A-form: at low humidity the DNA molecule will take the A-form: The A-form helix is wider and shorter, with a shorter more compact helical structure, than the B-form helix. Z-form: the Z-form DNA is adopted by short oligonucleotides. It is a left-handed double helix in which backbone phosphates zigzag.

Increasing degree of supercoiling Tertiary structure : Supercoils: double-stranded circular DNA form supercoils if the strands are underwound (negatively supercoiled) or overwound (positively supercoiled). Increasing degree of supercoiling Relaxed supercoiled

If the strands are overwound, form positively supercoiled; If the strands are underwound, form negatively supercoiled.

The DNA in a prokaryotic cell is a super coil. Super coiling makes the DNA molecule more compact thus important for its packaging in cells.

Eukaryotic DNA DNA in eukaryotic cells is highly packed. DNA appears in a highly ordered form called chromosomes during metaphase, whereas shows a relatively loose form of chromatin in other phases. The basic unit of chromatin is nucleosome. Nucleosomes are composed of DNA and histone proteins.

Nucleosome The chromosomal DNA is complexed with five types of histone. H1, H2A, H2B, H3 and H4. Histons are very basic proteins, rich in Arginine and Lysine. Nucleosomes: regular association of DNA with histones to form a structure effectively compacting DNA. ”beads”

Beads on a string 146 bp of negatively supercoiled DNA winds 1 ¾ turns around a histone octomer. H1 histone binds to the DNA spacer.

The importance of packing of DNA into chromosomes Chromosome is a compact form of the DNA that readily fits inside the cell To protect DNA from damage DNA in a chromosome can be transmitted efficiently to both daughter cells during cell division Chromosome confers an overall organization to each molecule of DNA, which facilitates gene expression as well as recombination.

Functions of DNA The carrier of genetic information. The template strand involved in replication and transcription. Gene: the minimum functional unit in DNA Genome: the total genes in a living cell or living beings.

What type of sugar is found in the nucleotides of DNA? deoxyribose ribose glucose Pentulose What is the role of hydrogen bonds in the structure if DNA? to code for proteins to synthesize proteins to separate the strands to connect the base pairs

Nucleoside is a pyrimidine or purine base covalently bonded to a sugar ionically bonded to a sugar hydrogen bonded to a sugar none of the above The sugar in RNA is ______ , the sugar in DNA is _____ deoxyribose, ribose ribose, deoxyribose ribose, phosphate ribose, uracil