DNA: Structure and its Features
Contents 1. The DNA Structure 2. Salient Features of DNA 3. Central Dogma 4. Packaging Of DNA helix
Brief History DNA as an acidic substance present in nucleus was first identified by Friedrich Meischer in 1869. He named it as 'Nuclein'. However, due to technical limitation in isolating such a long polymer intact, the elucidation of structure of DNA remained elusive for a very long period of time. It was only in 1953 that James Watson and Francis Crick, based on the X-ray diffraction data produced by Maurice Wilkins and Rosalind Franklin, proposed a very simple but famous Double Helix model for the structure of DNA One of the hallmarks of their proposition was base pairing between the two strands of polynucleotide chains. However, this proposition was also based on the observation of Erwin Chargaff that for a double stranded DNA, the ratios between Adenine and Thymine and Guanine and Cytosine are constant and equals one.
The DNA Structure DNA (Deoxyribonucleic acid) is a long polymer of deoxyribonucleotides. The length of DNA is usually defined as the number of nucleotides(or a pair of nucleotides usually referred to as base pairs). Each nucleotide in a chain of DNA has 3 components: A nitrogenous base, pentose sugar(ribose in case of RNA and deoxyribose in case of DNA) and a phosphate group There are two types of nitrogenous bases: Purines (Adenine and Guanine) and pyrimidine (Cytosine, uracil and thymine). Adenine, guanine, cytosine and thymine is present in DNA. Uracil is present in RNA instead of thymine. H2N H2G N-H N-H H-N H.N Guanine Adenine Cytosine Thymine Uracil Purines Pyrimidines
Nucleoside A nitrogenous base is linked to the pentose sugar through When a phosphate group is linked to 5'-OH of a nucleoside a N-glycosidic linkage to form a nucleoside, such as adenosine or deoxyadenosine, guanosine or deoxyguanosine, cytidine or deoxycytidine and uridine or present) is formed. deoxythymidine. Nucleotide through phosphoester linkage, a corresponding nucleotide (or deoxynucleotide depending upon the type of sugar Two nucleotides are linked through 3'-5' phosphodiester linkage to form a dinucleotide. More nucleotides join to form a polynucleotide chain A polymer thus formed has at one end a free phosphate moiety at 5'-end of ribose sugar, which is referred to as 5'-end of polynucleotide chain. Similarly, at the other end of the polymer the ribose has a free 3'-OH group which is referred to as 3' -end of the polynucleotide chain. The backbone in a polynucleotide chain is formed due to sugar and phosphates HO
Salient features of DNA One nucleotide Double H-bonds One nucleotide It is made of two polynucleotide chains, where the backbone is constituted by sugar-phosphate, and the bases project inside. 3OH 5P r (pentose) The two chains have anti-parallel polarity. It means, if one chain has the polarity 5, 3', the other has 3, 5'. Base The bases in two strands are paired through hydrogen bond (H-bonds) forming base pairs (bp). Adenine forms two hydrogen bonds with Ihymine from opposite strand and vice- versa. Similarly, Guanine is bonded with Cytosine with three H- bonds. As a result, always a purine comes opposite to a pyrimidine. This generates approximately uniform distance between the two strands of the helix Triple H-bonds 3 3 OH te Complementary base pairs Sugar-phosphate One polynucleotide chain H-bonds One polynucleotide chain Diagrammatic representation of Watson's and Crick's model of DNA
Contd.. (a) Complementary base pairing (b) The double helix (c)A space-filing model DNA: Salient backbone" of DNA Features The pitch of the helix is 3.4 nm (a nanometre is one billionth of a metre, that is 10-9 m) There are roughly 10 bp in each turn. Consequently, the distance between a bp in a helix is approximately equal to 0.34 nm base pairs joined by hydrogen bonding 3.4 nm The plane of one base pair stacks over the other in double helix. This in addition to H-bonds, confers stability of the helical structure Antiparallel strands their 5-to-3 polarities liein opposite directions) .
Central Dogma The proposition of a double helix structure for DNA and its simplicity in explaining the genetic implication became revolutionary. Very soon, Francis Crick proposed the Central dogma in molecular biology, which states that the genetic information flows from DNA RNA Protein. THE CENTRAL DOGMA AT GATCTCGTAA TACTAGAGCATT DNA RNA- Proteins Transcription Translation DNA TRANSCAIPTION mRNA AVGAUCUCGUAA Replication TRANSLATION Fig: Schematic Diagram of Central Dogma Ser STOP
Packaging of DNA Helix Need For Packaging of helix Taken the distance between two consecutive base pairs as 0.34 nm (0.34x10-9 m), if the length of DNA double helix in a typical mammalian cell is calculated (simply by multiplyingthe total number of bp with distance between two consecutive bp, that is, 6.6 109 bp 0.34 10-9m/bp), it comes out to be approximately 2.2 metres. A length that is far greater than the dimension of a typical nucleus (approximately 10-6 m). Therefore, to accommodate such long DNA helices there has to be some provision in the cell. DNA packaging in Prokaryotes In prokaryotes, such as, E. coli, though they do not have a defined nucleus, the DNA is not scattered throughout the cell. DNA (being negatively charged) is held with some proteins (that have positive charges) in a region termed as 'nucleoid'. The DNA in nucleoid is organised in large loops held by proteins
Packaging in Eukaryotes octamer of core histones: H2A, H2B, H3, H4 (each one x2) In eukaryotes, this organisation is much more complex. There is a set of positively charged, basic proteins called histones. Histones are rich in the basic amino acid residues lysines and arginines. Both the amino acid residues carry positive charges in their side chains. Histones are organised to form a unit of eight molecules called as histone octamer. The negatively charged DNA is wrapped around the positively charged histone octamer to form a structure called nucleosome. A typical nucleosome contains 200 bp of DNA helix. Nucleosomes constitute the repeating unit of a structure in nucleus called chromatin, thread-like stained (coloured) bodies seen in nucleus. The nucleosomes in chromatin are seen as 'beads-on- string' structure when viewed under electron microscope (EM) core DNA histone H1 linker DNA
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