Structure of DNA

Structure of DNA, TO TEACH FIRST YEAR MBBS STUDENTS

1. STRUCTURE OF D N A Part – 2 V.S. RAVI KIRAN

2. V.S.RAVIKIRAN, MSc., Department of Biochemistry, ASRAM Medical college, Eluru-534005.AP, India. [email protected]

3. STRUCTURE OF DNA Deoxyribonucleic acid (DNA) is composed of four deoxyribonucleotides , i.e. deoxyadenylate (A ), deoxyguany late ( G), deoxycytidylate (C ), and thymidylate (T).

4. STRUCTURE OF DNA These units are linked by 3′ to 5′ phosphodiester bonds to form a long polypeptide chain. The nucleotide is formed by a combination of base + sugar + phosphoric acid . The 3′-hydroxyl of one sugar is linked to the 5′- hydroxyl of another sugar through a phosphate group (Fig. 44.1).

5. STRUCTURE OF DNA In this particular example, the thymidine is attached to cytidine and then cytidine to adenosine through phosphodiester linkages (Fig. 44.1 ). Fig. 44.1: Polynucleotide

6. STRUCTURE OF DNA In the DNA, the base sequence is of paramount importance . The genetic information is encoded in the specific sequence of bases ; if the base is altered, the information is also altered.

7. STRUCTURE OF DNA The deoxyribose and phosphodiester linkages are the same in all the repeating nucleotides. Therefore , the message will be conveyed, even if the base sequences alone are mentioned as shown: 5′P--Thymine-- Cytosine-Adenine-3′OH Or , 5′------T--C--A---3′ This would convey all the salient features of the polynucleotide shown in Figure 44.1.

8. Polarity of DNA molecule In the case of DNA, the base sequence is always written from the 5 ′ end to the 3′ end. This is called the polarity of the DNA chain.

9. Watson-Crick Model of DNA Structure The salient features of Watson-Crick model of DNA are given in Figures 44.2 and 44.3. Fig. 44.2: Watson-Crick model of double helical structure of DNA. Adjacent bases are separated by 0.34 nm. The diameter or width of the helix is 2 nanometers.

10. Watson-Crick Model of DNA Structure Fig. 44.3: Base pairing rule. Base pairing of A with T and G with C. Hydrogen bonds between bases

11. Watson-Crick Model of DNA Structure Right Handed Double Helix DNA consists of two polydeoxyribonucleotide chains twisted around one another in a right handed double helix. The bases are located perpendicular to the helix axis, whereas the sugars are nearly at right angles to the axis.

12. Watson-Crick Model of DNA Structure The Base Pairing Rule Always the two strands are complementary to each other . So , the adenine of one strand will pair with thymine of the opposite strand, while guanine will pair with cytosine. The base pairing ( A with T; G with C ) is called Chargaff’s rule , which states that the number of purines is equal to the number of pyrimidines.

13. Watson-Crick Model of DNA Structure Hydrogen Bonding The DNA strands are held together mainly by hydrogen bonds between the purine and pyrimidine bases. There are two hydrogen bonds between A and T while there are three hydrogen bonds between C and G. The GC bond is therefore stronger than the AT bond.

14. Watson-Crick Model of DNA Structure The spatial alignment of the helix allows only purine to pyrimidine base pairing. A-T and C-G base pairs have almost the same shape. A mispairing will disturb the stable double helical structure.

15. Watson-Crick Model of DNA Structure Antiparallel The two strands in a DNA molecule run antiparallel, which means that one strand runs in the 5′ to 3′ direction, while the other is in the 3′ to 5′ direction. (Fig. 44.2). . (Fig. 44.2).

16. Watson-Crick Model of DNA Structure Other Features In the DNA, each strand acts as a template for the synthesis of the opposite strand during replication process. The spiral has a pitch of 3.4 nanometers per turn. Within a single turn , 10 base pairs are seen. Thus , adjacent bases are separated by 0.34 nm. The diameter or width of the helix is 1.9 to 2.0 nm.

17. Watson-Crick Model of DNA Structure A major groove ( 1.2 nm) and a minor groove ( 0.6 nm) wind along the molecule, parallel to the phosphodiester backbone. In these grooves, proteins interact with the exposed bases.

18. Watson-Crick Model of DNA Structure The stacking of base pairs stabilize the double helix by the hydrophobic effect and conformation of the ring systems. DNA is the storehouse of genetic information (Box 44.1).

19. Watson-Crick Model of DNA Structure

20. Denaturation of DNA Strands Denaturation of DNA Strands The double stranded DNA may be denatured and separated by heat. This is called as melting of DNA . Tm or melting temperature is the temperature when half of the helical structure is denatured . At lower temperature, the melted strands are re-associated; this is called annealing . When DNA is denatured, unstacking of bases occur resulting in increased absorbance at 2 6 nm - hyp erc hro mic ity .

21. Higher Organization of DNA In higher organisms, DNA is organized inside the nucleus. Double stranded DNA is wound round histones to form nucleosomes (Fig. 44.4). Fig. 44.4: DNA wraps twice around histone octamer to form one nucleosome

22. Chromatin Chromatin is a loose term employed for a long stretch of DNA in association with histones . Chromatin is then further and further condensedto form chromosomes ( Fig. 44.5). Similarly , the DNA molecule is folded and compressed to 10,000 fold to generate chromosomes (Fig.44.5). Fig. 44.5: DNA condenses repeatedly to form chromosome

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