Introduction to Organic and Biochemistry (CHE 124) Reading Assignment General, Organic, and Biological Chemistry: An Integrated Approach 3 rd. Ed. Ramond Chapter 13 Nucleic Acids

Central Dogma of Molecular Biology DNA  RNA  Protein mRNA. tRNA, rRNA, snRNA Nucleus –Replication - DNA directed DNA synthesis –Transcription - DNA directed RNA synthesis ·Processing of mRNA capping, polyadenylation, splicing Cytoplasm –Translation - RNA directed Protein synthesis Transcription Translation Replication

Nucleic Acids Nucleic Acid - linear, non-branched polymer of nucleotides Classes of Nucleic Acids –RNA = ribonucleic acid –DNA = 2' deoxyribonucleic acid

Functions of Nucleic Acids Building blocks of DNA and RNA –DNA = Genetic material –RNA = Adapter molecule between DNA and protein Transport chemical energy within the cell –ATP Signal molecule  cyclic AMP

Nucleotide Nucleotide contains: –Pentose sugar –Nitrogenous base –Phosphate –One or more Adenosine Triphosphate (ATP)

Nucleotide phosphate group

Pyrimidine Bases Cytosine (C ) 4-amino-2-oxypyrimidine DNA and RNA Thymine (T) 5-methyl-2,4-dioxypyrimidine DNA ONLY Uracil (U) 2,4-dioxypyrimidine RNA ONLY Pyrimidine

Purine Bases Adenine (A) 6 – aminopurine DNA and RNA Guanine (G) 2- amino-6-oxypurine DNA and RNA Purine

Sugar Phosphate Backbone Nucleotides connected by 3’ to 5’ phosphodiester bond –Imparts uniform negative charge to DNA / RNA Negative charge repels nucleophilic species (e.g. hydroxyl) thus the phosphodiester bond resists hydrolytic attack. Separation by agarose gel electrophoresis –Creates 3’ and 5’ end (directionality) Convention: Nucleotide sequences are written 5’ to 3,’ L to R

Bases are attached to sugar by Beta Glycosidic linkage N-9 of purine and N-1 of pyrimidine

Nucleotide Nucleoside = sugar + nitrogenous base, Nucleotide = sugar + nitrogenous base + phosphate. Adenosine monophosphate (A nucleotide) Adenosine (A nucleoside)

Watson and Crick (Complementary) Base Pairing A T G C Nucleotide content determines melting point of DNA.

DNA is Organized into Genes Gene –discrete, functional unit of DNA –when expressed, (transcribed) yields a functional product rRNA, tRNA, snRNA mRNA - translated into a polypeptide sequence. –Open reading frame - long stretch of nucleotides that can encode polypeptide due to absence of stop codons.

Double Helix B form –Diameter of helix = 20.0 Å (2.00 nm) –10.4 base pairs / turn; 34 Å (3.4 nm) –1 base pair 3.4 Å (0.34 nm) Note –Complementary base pairing –Major grove –Minor grove –Antiparallel –Hydrogen bonding between complementary base pairs.

Chromatosomes Pack to Form Chromatin Fibers Histones H1, H2A, H2B, H3, H4 Histones contain (>20%) arg and lys ---basic amino acids

Karyotype Photograph of chromosomes from a single organism Arranged by size (largest to smallest) Homo sapiens –46 chromosomes –23 pairs 3 billion base pairs (hapliod) 25,000 genes

Types of RNA –Ribosomal RNA (rRNA)– part of the ribosome –Transfer RNA (tRNA) - –Messenger RNA (mRNA)– sequence translated into protein sequence. –Small nuclear RNA (snRNA) – involved in splicing (spliceosome) –Micro RNA (mi RNA) – small RNA complementary to mRNA that inhibits translation of the mRNA –Small interfering RNA (siRNA) – small RNA that binds to mRNA causing destruction of mRNA

RNA molecules are complementary to the DNA template. mRNA is complementary to template strand mRNA is identical (except for U to T changes) to the coding strand.