Saturday, February 28, 2009

DNA

Deoxyribose Nucleic Acid

DNA is present in all plant cells, animals, few prokaryotes and in a number of viruses. In eukaryotes it is combined with proteins to form nucleoproteins. In prokaryotes it is without any proteins. The DNA of all plants and animals and many viruses is double stranded. In the bacteriophage phi 174, however it is single stranded.

The widely accepted molecular model of DNA is the double helix structure proposed by Watson and Crick. The DNA molecule consists of two helically twisted strands connected together by ‘steps’. Each strand consists of alternating molecules of deoxyribose (a pentose sugar) and phosphate groups. Each step is made up of a double ring purine base and single ring pyrimidine base. The purine and pyrimidine bases are connected to deoxyribose sugar molecules. The two strands are intertwined in a clockwise direction i.e., in a right hand helix and run in opposite directions. The twisting of the strands results in the formation of deep and shallow spiral grooves.

The DNA molecule is a polymer consisting of several thousand pairs of nucleotide monomers. Each nucleotide consists of the pentose sugar deoxyribose, a phosphate group and a nitrogenous base which may be either a purine or a pyrimidine. Deoxyribose and a nitrogenous base together for a nucleoside and a nucleoside with a phosphate together form a nucleotide.

Deoxyribose is a pentose sugar with five carbon atoms. Four of the five carbon atoms plus a single atom of oxygen form a five-membered ring. The fifth carbon atom is outside the ring and forms a part of a –CH2 group. The four atoms of the ring are numbered 1’, 2’, 3’ and 4’. The carbon atom of the –CH2 is numbered 5’. There are three –OH groups in positions 1’, 3’ and 5’. Hydrogen atoms are attached to carbon atoms 1’, 2’, 3’ and 4’.

Ribose the pentose sugar of RNA, has an identical structure except that there is an –OH group instead of H on carbon atom 2’. All the sugars of one strand are directed to one end, i.e, the strand has polarity. The sugars of the two strands are directed in opposite directions.

Nitrogen bases: there are two types of nitrogenous bases, pyrimidines and purines. The pyrimidines are single ring compounds, with nitrogen in positions 1’ and 3’ of a 6 membered benzene ring. The two most common pyrimidines of DNA are cytosine and thymine. The purines are double ring compounds. A purine molecule consists of a 5-membered imidazole ring joined to a pyrimidine ring at position 4’ and 5’. The two most common purines of DNA are adenine and guanine.

Base Paring: Each step of the DNA ladder is made up of a purine and a pyrimidine pair, i.e., of a double ring and a single ring compound. Two purines would occupy too much space, while two pyrimidines would occupy too little. Because of the purine-pyrimidine pairing the total number of purines in a double stranded DNA is equal to the total number of pyrimidines. Thus A/T = 1 and G/C = 1 or A+G = C+T. The ratio of A+T/G+C, however, rarely equals to 1, and varies with different species from 0.4 to 1.9. The purine and pyrimidine bases pair only in certain combinations. Adenine pairs with thymine and guanine with cytosine. A and T are joined by two hydrogen bonds through atoms attached to positions 6’ and 1’. Cytosine and guanine are joined by three hydrogen bonds through positions 6’, 1’ and 2’. The pyrimidine and purine bases are linked to the deoxyribose sugar molecules. The linkage in pyrimidine nucleosides is between position 1’ of deoxyribose and 3’ of the pyrimidine. In purine nucleosides it is between position 1’ of deoxyribose and position 9’ of the purine.

Phosphate: In the DNA strand the phosphate group alternate with deoxyribose. Each phosphate is joined to carbon atom 3’ of one deoxyribose and to carbon atom 5’ of another. Thus each strand has a 3’end and a 5’ end. The 3’ end of one strand corresponds to the 5’ end of the other. Consequently the oxygen atoms of deoxyribose point in opposite directions in the two strands.

Forms of DNA: DNA can exist in the A. B. C and D forms. Sugar puckering is the most important characteristic for distinguishing the DNA forms. The A form has 3’-endo puckering and one turn of the helix consists of 11 base pairs (11-fold helix). The B form is with 3’-exo puckering and 10 base pairs (basic structure proposed by Watson and Crick). C form is with 2’-endo puckering with a helical symmetry of 91/3 i.e., there are fewer residues per turn than in the B form. The D form is with 3’-exo puckering with 8 base pairs per turn of the helix.

RL helix and Z DNA: According to the Watson and Crick model DNA exists in the form of right handed helix. But G.A. Rodley’s group working in New Zealand and V. Sasisekharan’s group working in India have independently proposed a structure of B-DNA radically different from the Watson and Crick model. According to them, the DNA duplex is formed by alternating right and left handed helices arranged side by side. Each strand of the DNA duplex has 5 base pairs in the right handed helix alternating with 5 base pairs in the left-handed helix.

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