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DNA and protein synthesis: DNA structure

What is DNA?

  

DNA stands for DeoxyriboNucleic Acid and carries genetic information in cells. In eukaryotic cells most DNA is found in the nucleus as linear chromosomes, with some circular chromosomes in organelles. This extranuclear DNA includes mitochondrial DNA and plastid DNA. In prokaryotic cells chromosomal DNA is circular and is found in a nucleoid consisting of DNA, RNA and protein. Most prokaryotic cells have plasmids, circular DNA which replicates independently from the chromosomal DNA and can sometimes be passed between organisms during conjugation. Information in DNA includes not only genes to be transcribed but also binding regions for inhibitor or promoter proteins which regulate the amount and timing of gene expression.

 

Basic Structure of DNA

 

The building blocks of DNA are four nucleotides; the purines Adenine (A) and Guanine (G) and the pyrimidines Cytosine (C) and Thymine (T). These are joined together in long strange by covalent phosphodiester bones. In DNA two strand join non-covalently through hydrogen bonds between complimentary base pairs (A+T and C+G) to form two stranded DNA. This coils into a right handed helix with ten nucleotides per turn of the helix. The bases point into the center of the helix with a phosphate backbone around the outside which gives DNA a negative charge. The helix contains major and minor grooves due to the way it twists. Major grooves have more H bond acceptors and donors (O and N, and H respectively) exposed than minor grooves.

 

Two strands will only pair if they are complementary, meaning that the complimentary base pairs line up. For example the sequence AAAA is complimentary to TTTT but not to itself or GGGG. Strands are in an antiparallel orientation; 5' carbon of one nucleotide binds to 3' carbon of adjacent nucleotide - this is oppositely orientated on each opposing strand, 5' -> 3' and 3' -> 5' directions.

 

What Does DNA Look Like?

Base PairingHelical Structure

The DNA Sequence

 

To sequence genomes, Allan Maxam and Walter Gilbert made the Maxam-Gilbert method, or chemical method.  This involves chemicals cleaving DNA at specific base sequences.

Another method, called the Sanger or chain termination method, involves dideoxynucleotides interfering with DNA enzymatic synthesis.

Genomes differ from person to person commonly by SNPs or single nucleotide polymorphisms.  If SNPs occur close together on a chromosome, they usually become inherited together in haplotypes.  Genomes also differ by DNA duplications, deletions, and rearrangements.

Eukaryotic genomes contain lots of repeated sections of DNA.  This property makes eukaryotic genomes very large.  For instance, the human genome is 3200 Mb (mega base) long.

One type of repeat includes tandem repeats.  These account for about 10 - 15% of mammalian genomes which includes many types of sequences of DNA.  One repeated unit can vary 1 - 2000 bp (base pairs) in length.  Most units are 10 bp or less - simple-sequence DNA repeats.  

These types of sequences will not usually be transcribed (made into RNA) but may account for creating certain physical properties at particular regions on a chromosome - they are usually found at the centromere.  Telomeres also contain simple-sequence repeats.

Another type of repeat includes interspersed repeats.  These repeats are spread across the genome.  Different kinds include transposable elements, LINEs, and SINEs.

 

Human Chromosomes

http://www.edinformatics.com/math_science/human_genome.htm

DNA Packaging

In Bacteria

  • May have circular, linear, or multiple chromosomes - most commonly circular
  • When bound to proteins, localise to the nucleoid of the cell
  • DNA here arrange into threadlike / fibre mass
  • Chromosomes are negatively supercoiled and folded into loops
  • Thought that loops are held in position by protein and RNA
  • Plasmids may also be present
  • These are supercoiled, allowing them to be compact
  • They replicate autonomously
  • Plasmids can be F (fertility) or R (resistance) factors, col (colicinogenic) factors, virulence factors, metabolic plasmids, or cryptic plasmids

 

 

 

    In Eukaryotes

    • Chromosomes are large, linear and single DNA molecules
    • DNA gets converted to chromatin which are scattered through the nucleus
    • Chromatin then gets condensed into chromosomes at cell division
    • Histones bind to DNA
    • There are 5 main types of histones - H1, H2A, H2B, H3, and H4
    • DNA wrapped around histones is known as 'bead-on-a-string' structure, each bead called a nucleosome
    • In intact cells, get 30-nm chromatin fibre
    • Folding of this gives looped domains
    • Next level up is heterochromatin or euchromatin
    • Each chromosome is then composed of two chromatids - this is even more condensed than the previous chromatin packaging molecules

     

     

     

     

        Eukaryotic DNA Packing



        DNA vs RNA

        DNA

        1. Deoxyribonucleic Acid
        2. Storage of genetic information
        3. Double stranded - antiparallel and parallel strands
        4. Contains A, T, C, and G bases
        5. Contains a deoxyribose pentose sugar
        6. Bases on opposing strands are held together by hydrogen bonds
        7. Usually present in the nucleus of the cell - some is in mitochondria and chloroplasts for example
        8. SNPs etc provide genetic variation between individuals of a particular species

         

         

         

          RNA

          1. Ribonucleic Acid
          2. Transporter/Messenger of genetic information
          3. Single Stranded (usually)
          4. Contains U instead of T
          5. Contains a ribose pentose sugar
          6. Bases exist as codons (sets of 3)
          7. Travels from the nucleus to the cytoplasm
          8. Mainly exists as messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA)
          9. Can also exist as specialised RNAs including microRNA (miRNA), small interfering RNA (siRNA), and long non-coding RNA (lncRNA)

           

           

           

            Extra Information!

             

            Different Types of DNA

            B-DNA = right handed - most common type in the cell

            Z-DNA = left handed - long, thin, biological significance relatively unknown

            A-DNA = also right handed but shorter and thicker than B-DNA - created by dehydrating the B-DNA

             

             

            Definitions

             

            Centromere = region that holds together sister chromatids before anaphase

            Chromatin = DNA-protein complex fibres that chromosomes are made up of

            Chromosome = a single molecule of DNA found in eukaryotes

            col (colicinogenic) factor = enable bacteria to secrete compounds (colicins) which kill col factor-lacking bacteria

            Cryptic plasmid = unknown function

            Euchromatin = in interphase, a type of loose and uncondensed DNA-containing chromatin

            F (fertility) factor = involved in conjugation

            Genome = the DNA which is a complete copy of total genetic information of an organism/virus. To sequence a genome, a number of methods can be used

            Haplotype = SNP group positioned near each other on a chromosome, usually inherited together

            Heterochromatin = in interphase, a type of compact DNA-containing chromatin

            LINEs = long interspersed nuclear elements - 6000 - 8000 bp long repeated DNA sequence

            Metabolic plasmid = allow metabolic reactions to take place by producing certain enzymes

            Purines = nitrogen-containing, two-ringed molecule

            Pyrimidines = nitrogen-containing, one-ringed molecule

            R (resistance) factor = drug resistant gene carriers

            SINEs = short interspersed nuclear elements - > 500 bp long & relies on enzymes for movement

            Single nucleotide polymorphisms = change in a single base in DNA which takes place between individuals of a particular species

            Supercoiled = when DNA twists upon itself

            Telomere = sequences of DNA at the end of a eukaryotic chromosome which can be broken down by telomerase

            Telomerase = enzyme which carries out catalysis of forming extra copies of telomeric repeat sequences

            Transposable elements = or transposon, sequence of DNA that can move to different chromosome locations

            Virulence factor = allow bacteria to enter the host cells by enabling bacteria to produce toxic proteins, leading to disease

             

             

            References

             

            W. M. Becker, L. J Kleinsmith, J. Hardin, G. P. Bertoni (2009) The World of the Cell (7th ed.) San Fransisco : Pearson Education, Inc., chap. 18 ; pg 513 - 538

            H. R. Horton, L. A. Moran, K. G. Scrimgeour, M. D. Perry, J. D. Rawn (2006) Principles of Biochemistry (4th ed.) New Jersey : Pearson Education, Inc., chap 19 ; pg 583 -604

            Human Chromosomes Picture from University of Leicester (n/a) DNA, genes, and chromosomes [online] http://www2.le.ac.uk/departments/genetics/vgec/education/under18/topics/dnageneschromosomes Creative Commons Licence [Accessed on 02/04/2012]

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