Nucleic Acid Structure & Function

Biomedical Importance Genetic information is coded along the length of a polymeric molecule composed of only four types of monomeric units This polymeric molecule, DNA, is the chemical basis of heredity and is organized into genes, the fundamental units of genetic information. The basic information pathway DNA directs the synthesis of RNA, which in turn directs protein synthesis Genes do not function autonomously; their replication and function are controlled by various gene products, often in collaboration with components of various signal transduction pathways.

Biomedical Importance Knowledge of the structure and function of nucleic acids is essential in Understanding genetics and many aspects of pathophysiology as well as the genetic basis of disease.

The interrelationship of DNA,RNA & Protein

DNA CONTAINS THE GENETIC INFORMATION DNA can Transform Cells DNA Contains Four Deoxynucleotides deoxyadenylate, deoxyguanylate, deoxycytidylate, and thymidylate Monomeric units of DNA are held in polymeric form by 3′,5′-phosphodiester bridges constituting a single strand The informational content of DNA (the genetic code) resides in the sequence in which these monomers are ordered.

Polynucleotides Are Directional Macromolecules The polymer possesses a polarity one end has a 5′-hydroxyl or phosphate terminal the other has a 3′-phosphate or hydroxyl terminal. 5' -terminus & 3' –terminus

Polynucleotide representation The base sequence or primary structure of a polynucleotide can be represented as The phosphodiester bond is represented by P or p, bases by a single letter, and pentoses by a vertical line.

Polynucleotide representation More compact notation pGpGpApTpCpA The most compact representation shows only the base sequence GGATCA 5′- end is at the left, and all phosphodiester bonds are 3′ → 5′.

Oligonucleotides, Nucleic acids containing ≤ 50 nucleotides Polynucleotides those that are longer Mononucleotides (nucleoside monophosphates) linked by 3′ → 5′- phosphodiester bonds Polynucleotides may be RNA Contain Ribonucleosides & uridine (U) DNA Deoxyribonucleosides & deoxythymidine (dT)

Polynucleotides may be Single strand Double strand Linear or circular

a single-stranded DNA sequence held together by a phosphodiester backbone between 2′- deoxyribosyl moieties attached to the nucleobases by an N- glycosidic bond. the backbone has a polarity (ie, a direction)

STRUCTURE OF DNA DNA is a double-stranded helix The two strands held together by hydrogen bonds Each strand of which possesses a polarity, antiparallel; one strand runs in the 5′ to 3′ direction and the other in the 3′ to 5′ direction. The pairings between the purine and pyrimidine nucleotides on the opposite strands are very specific and are dependent upon hydrogen bonding of A with T and G with C

the concentration of deoxyadenosine (A) nucleotides equals that of thymidine (T) nucleotides (A = T), while the concentration of deoxyguanosine (G) nucleotides equals that of deoxycytidine (C) nucleotides (G = C)

Double-Helical DNA

The structure of a G-quartet. The four coplanar guanines form a tetrameric structure by formation of Hoogsteen hydrogen bonds. The cavity in the cenrer of [he quartet can accommodate a sodium or potassium ion with coordination by the four 0-6 oxygens.

extent of DNA packaging in metaphase chromosomes

Types of sequences in the human genome.

Requirements for DNA Replication

Classes of proteins involved in replication

DNA provides a template for Replication & transcription

DNA replication is semiconservative

Steps involved in DNA replication in eukaryotes

DNA polymerase III

The initiation of DNA synthesis upon a primer of RNA

A comparison of prokaryotic and eukaryotic DNA polymerases

The telomere replication problem

Cell cycle

Bacterial promoters

Promoter structure

Bacterial promoters

Eukaryotic Promoters Are More Complex

the transcription control regions

Structure of a typical eukaryotic mRNA showing elements that are involved in regulating mRNA stability

Classes of eukaryotic RNA.

Nomenclature and properties of mammalian nuclear DNA-dependent RNA polymerases.