molecular genetics

A group of chemicals in cell that allow the transmission of inherited information. polymers of nucleotides DNA – deoxyribose nucleic acid RNA - ribose nucleic acid

Nucleic acids are the genetic material of the cell and are composed of recurring monomeric units called nucleotides Each nucleotide is comprised of three principal components: 5-carbon pentose sugar (pentagon) Phosphate group (circle) Nitrogenous base (rectangle) Both the phosphate group and nitrogenous base are attached to the central pentose sugar The nitrogenous base is attached to the 1’– carbon atom (right point) The phosphate base is attached to the 5’– carbon atom (left point)

Made up of: a carbon sugar (ribose or deoxyribose) a phosphate group a nitrogen base (guanine, adenine, thymine, cytosine, uracil) The bonds within the nucleotide are covalent bonds.

The phosphate groups join nucleotides together by bonding the C3 of one sugar with the C5 of an adjacent sugar.

C and G bond in DNA and RNA A and T bond in DNA A and U bond in RNA The base pairs are held by weak hydrogen bonds.

Deoxyribose nucleic acid DNA carries the genetic message for the functioning of the organism. A gene is a length of DNA that codes for a polypeptide, which forms a protein. So DNA codes for the synthesis of proteins.

Chromosomes in the nucleus of eukaryotes and in the plastids of prokaryotes In mitochondria In chloroplasts

The 5-carbon sugar is deoxyribose. The sugars are labelled 1’ to 5’. The shape of the molecule is a twisted ladder called a double helix. The sides of the ladder are made of deoxyribose – phosphate – deoxyribose - phosphate etc. The rungs of the ladder are made up of two bases which always pair adenine with thymine (A-T) and guanine with cytosine (G-C)

The two nucleotide strands of DNA run in opposite directions (called anti-parallel). (5’ – 3’ down one strand and 3’ – 5’ down the other). One turn of the helix contains 10 nucleotides. Three DNA bases (called a triplet) code for one amino acid

The two nucleotide strands of DNA run in opposite directions (called anti-parallel). (5’ – 3’ down one strand and 3’ – 5’ down the other). One turn of the helix contains 10 nucleotides. Three DNA bases (called a triplet) code for one amino acid

Viruses 5-200 kilo base pairs (kb) Bacteria 500-5000 kb Yeast 13,500 kb Fruit fly 165,000 kb Human 2,900,000 kb

The structural organisation of the DNA molecule was correctly proposed in 1953 by James Watson and Francis Crick • constructed models to quickly visualise and assess the viability of potential structures • Their efforts were guided by an understanding of molecular distances and bond angles developed by Linus Pauling, and were based upon some key experimental discoveries:

Using trial and error, Watson and Crick were able to assemble a DNA model that demonstrated the following: DNA strands are antiparallel and form a double helix DNA strands pair via complementary base pairing (A = T ; C Ξ G) Outer edges of bases remain exposed (allows access to replicative and transcriptional proteins)

The first model generated was a triple helix Early models had bases on the outside and sugar-phosphate residues in the centre Nitrogenous bases were not initially configured correctly and hence did not demonstrate complementarity

The final construction of a correct DNA molecule owed heavily to the X-ray crystallography data generated by Franklin This data confirmed the arrangement of the DNA strands into a helical structure The data was shared without Franklin’s knowledge or permission and contributed profoundly to the final design Hence, Franklin is now recognised as a key contributor to the elucidation of DNA structure

Prokaryote – circular Eukaryote – DNA wound around histone proteins – bead like, made up of 8 molecules. There are other histones on the outside of the DNA. Collectively known as a nucleosome. To avoid tangling, DNA needs to be coiled into chromosomes for cell division. To do this, the beaded nucleosomes coil tightly to form chromatin fibres. Looped domains form and these attach to non-histone protein structures. The looped domains coil and fold further to form chromosomes.

coding regions on DNA – code for proteins Only about 10% of the human genome are exons.

non-coding regions on DNA Some introns are used as regulators of gene expression, as telomeres and genes for tRNAs. Most introns seem to have no function at all. During protein synthesis the introns are edited out so that only coding regions (exons) are used.

regions of repetitive DNA located at each end of a chromatid and function to prevent chromosomal deterioration

During DNA replication, the extreme ends of the telomere cannot be copied and so the telomere gets marginally shorter - This occurs because the terminal RNA primer on the lagging strand cannot be replaced (no 3’-attachment point for DNA pol I) The progressive shortening of telomeres is associated with ageing (senescence), age-related diseases and mortalilty

Telomeres can be lengthened by the enzyme telomerase, allowing for continued cell division past the Hayflick limit Permanent activation of telomerase can cause cells to become immortal and leads to cancer (uncontrolled cell division) Many cancer researchers are currently investigating the viability of telomerase inhibitor drugs as a treatment for cancers

Cells have a limited capacity for cellular division • Hayflick limit = ~ 40 – 60 divisions for a typical human cell

Introns often constitute highly repetitive sequences (tandem repeats) that may make up almost 50% of the genome. Typically between 5 and 300 base pairs per repeat and may be duplicated as many as 105 times. These regions used to be referred to as ‘junk DNA’. Tandem repeats are used in DNA profiling because they are highly variable.

RIBOSE NUCLEIC ACID - RNA Differs from DNA: Sugar is ribose instead of deoxyribose. Base uracil instead of thymine. Single strand instead of double helix. Less stable than DNA Much smaller (DNA is a thousand to a million times larger).