Molecular Basis of Inheritance NUCLEIC ACIDS

NUCLEIC ACIDS

1. F. Meischer discovered nucleic acid in nucleus of pus cell and called it "nuclein". The term nucleic acid was coined by "Altman".

2. Nucleic acids are polymer of nucleotides.

Example: DNA and RNA.

Nucleotide= Nitrogen base + Pentose sugar + phosphate.

Nucleoside= Nitrogen base + Pentose sugar.

A. Nitrogen base: 

On the basis of structure nitrogen bases are broadly of two types:- 

1. Pyrimidines- consist of one pyrimidine ring. Skeleton of ring composed of two nitrogen and four carbon atoms. e.g. Cytosine, Thymine and  Uracil.

 2. Purines- consist of two rings i.e. one pyrimidine ring (2N+4C)  and one imidazole ring (2N+3C) e.g. Adenine and Guanine.

B. Pentose sugar (Number of carbon= 5):-

C. Phosphate:

-Acidic

-Negative charged

Nitrogen base froms bond with first carbon of pentose sugar to form a nucleoside. Nitrogen of first place (N1) forms bond with sugar in case of pyrimidines while in purines nitrogen of ninth place (N9) forms bond with sugar.

Phosphate forms ester bond (covalent bond) with fifth carbon of sugar to form a complete nucleotide.

Types of Nucleosides and Nucleotides

1. Adenine+Ribose=Adenosine

Adenosine+Phosphate=Adenylic acid (AMP).

2. Adenine+Deoxyribose=Deoxy adenosine

Deoxyadenosine+P=Deoxyadenylic acid (dAMP).

3. Guanine+Ribose=Guanosine

Guanosine+P=Cytidylic acid (CMP).

4.Guanine+Deoxyribose=Deoxy Guanosine

Deoxy Guanosine+P= Deoxy guanylic acid (dGMP).

5. Cytosine+Ribose=cytidin

Cytidine+P=Cytidylic acid (CMP).

6. Cytosine+Deoxyribose=Deoxycytidine

Deoxycytidine+P=Deoxycytidylic acid (dCMP).

7. Uracil+Ribose=Uridine 

Uridine+P=Uridylic acid (UMP).

8.Thymine+Deoxyribose=Deoxy thymidine

Deoxycytidine+P= Deoxythymidylic acid (stamp).

DNA

1.DNA as an acidic substance present in nucleus was first identified by Friedrich Meischer in 1869.

2. DNA term was given by Zacharis.

3. DNA is long polymer of deoxyribonucleotides.

4. DNA is negatively charged.

5. In DNA pentose sugar is Deoxyribose sugar and for types of nitrogen bases A,T,G,C.

6. Wilkins and Franklin studied DNA molecule with help of X-Ray cyrstallography.

7. With the help of this study, Watson and Crick (1953) proposed a double helix model for DNA. For this model Watson, Crick and Wilkins were awarded by Nobel Prize in 1962.

8. One main hallmark (main point) of double helix model is complementary base pairing between purine and pyrimidine.

9. According to this model, DNA is composed of two polynucleotide chains.

10. Both polynucleotide chains are complementary and antiparallel to each other.

11. In both strand of DNA direction of phosphodiester bond is opposite. i.e. If direction of phosphodiester bond in one strand is 3'-5' then it is 5'-3' in another strand.

12. Both strand of DNA are held together by hydrogen bonds. These hydrogen bonds are present between nitrogen bases of  both  strand. 

13. Adenine binds to thymine by two hydrogen bonds and Cytosine binds to guanine by three hydrogen bonds. 

14. In a DNA molecule one purine always pairs with pyrimidine. This generates approximately uniform distance between the two strand of DNA.

15. In DNA plane of one bases pair stacks over the other in double helix. This, in addition to H-bonds, confers stability of the helical structure of DNA.

16. Chargaff's equivalency rule- In double stranded DNA amount of purine nucleotides is equals to amount of pyrimidine Nucleotides.

Purine=Pyrimidine

 [A]+[G]

------------ =1

 [T]+[C] 

17. Base ratio:- 

 A+T

------ = constant for given species. i.e         

G+C                 species specific.

18. In DNA A+T>G+C = A-T type DNA. Base ratio of A - T type of DNA is more than one. Eg. Eukaryotic DNA.

19. In a DNA G+C>A+T= G-V type DNA. Base ratio of G - C type of DNA is less than one.

Eg. Prokaryotic DNA.

20. Melting point of DNA depends on G-C contents.

More G-C contents means higher melting point.

Tm= Temperature of melting.

Tm of prokaryotic DNA>Tm of Eukaryotic DNA.

21. DNA absorbs U.V. rays of 2600A° wavelength.

22. Denaturation and renaturation of DNA - If a normal DNA molecule is placed at high temperature (80-90°c) then both strands of DNA will separate from eachother due to breaking of hydrogen bonds. It is called DNA-denaturation. 

23. When denatured DNA molecule is placed at normal temperature then both strand of DNA attached and recoiled to each other. It is called renaturation of DNA.

Configuration of DNA molecules:-

1. Two strands of DNA are helically coiled like a revolving ladder. Backbone of this ladder (Reiling) is composed of phosphates and sugars while steps (bars) are composed of pairs of nitrogen bases.

Two chains have anti-parallel polarity. It means, if one chain has the polarity 5'-3', the other has 3'-5'.

2. Distance between two successive steps is 3.4A°. In one complete turn of DNA molecule there are such 10 steps (10 pairs of nitrogen bases). So the length of one complete turn is 34A°. This is called helix length.

3. Diameter of DNA molecule i.e. distance between phosphates of two strands is 20A°.

4. Each step of ascent is represented by a pair of bases. At each step of ascent, the strand turns 36°.

5. In nucleus of Eukaryotes the DNA is associated with histone protein to form nucleoprotein.

6. Bond between DNA and Histone is salt linkage (Mg+2).

ϕ ×174 (bacteriophage) [single stranded] - 5386 Nucleotides.

λ bacteriophage - 48502 base pair.

E. Coli - 4.6× 10^{6  base pair.}

Human - 6.6× 10^{9  base pair.}

^{Types of DNA:-}

^{On the basis of direction of twisting, there are two types of DNA.}

1. Right Handed DNA- clockwise twisting e.g. the DNA for which Watson and Crick proposed model was 'B'DNA.

2. Left Handed DNA- Anticlockwise twisting e.g. Z-DNA - Discovered by Rich. Phosphate and sugar backbone is zig-zag.

Helix length - 45.6 A°.

^{Diameter - 18.4 A°.}

^{No. Of base pairs - 12 (6 dimers).}

^{Distance between 2 bases pairs - 3.75 A°.}

^{Palindromic DNA- Wilson and Thomas.}

 →

CC   GG  TA  CC  GG

GG   CC  AT  GG  CC 

                                 ← 

Sequence of nucleotides same form both ends.

PACKAGING OF DNA HELIX

The average distance between the two adjacent base pairs of 0.34 nm (0.34 x 10^–9 m or 3.4 A°). Length of DNA for human diploid cell is 6.6.x 10^–9 bp x 0.34 x 10^–9 m/bp =2.2m. The length is far greater than the dimension of typical nucleus (approximately 10^–6 m).  The number of bade pairs in Escherichia coli is 4.6×10⁶ . The total length is 1.36 mm. The long sized DNA accommodated in small area (about 1  μm in  E. coli) only through packing of compacted. DNA s acidic due to presence of large number of phosphate group. Compaction occurs by folding acid attachment of DNA with basic proteins, polyamine in prokaryotes and histone in eukaryotes.

DNA packaging in Prokaryotes : DNA is found in cytoplasm in supercoiled state. The coils and maintained by non histone basic protein like polyamines. This compact structure of DNA is called nucleoid genophore.

DNA packaging in Eukaryotes: It is carried out with the help of lysine and arginine rich basic proteins called histone. The unit of compaction is nucleosome. There are five types of histone proteins H1,H2A,H2B,H3 and H4.  

Four of them occur in pairs to produce histone octamer (2 copies of each- H2A,H2B,H3 and H4), called nubody or  core of nucleosome. Their positively charged ends are directed outside. 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. DNA present between two adjacent nucleosome is called linker DNA. It is attached to H1 histone protein. Length of linker DNA varies from species to species. Nucleosome chain gives a beads on string appearance under electron microscope. The nucleosomes furthers coils to form solenoid. It has diameter  of 30 nm as found in chromatin The beads on string structure in chromatin is packaged to  form chromatin fibres that are further coiled and condensed at metaphase stage of cell division to form chromosomes. The packaging at higher level requires additional set of proteins (acidic) that collectively are referred to as non histone chromosomal (NHC) Proteins.

Non-Histone chromosomal proteins are of three types:

1.Structural NHC protein.

2.Functional NHC protein e.g. DNA polymerase, RNA polymerase.

3.Regulatory NHC protein

In a typical nucleus, some region of chromatin are loosely packed (and stains light) and are referred to as euchromatin. The chromatin that is more densely packed and stains dark is called as heterochromatin, specifically euchromatin is said to be transcriptionally active and heterochromatin is transcriptionally inactive.

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