Nucleic acids

Nucleic acids are of polymers of nucleotides. Before studying nucleic acids, let’s look at nucleotides, nucleotides, purines and pyrimidines.

Nucleotides

They come in 8 different varieties

Structure: A nitrogenous base linked to a sugar. At least one phosphate group needs attachment with the sugar. 

Nitrogenous Base+ Sugar+ Phosphate= Nucleotide

In DNA, the sugar is 2’- deoxyribose (no hydroxyl group on the carbon atom at position 2)

In RNA, the sugar is ribose 

The phosphates are acidic and make the nucleic acid a polyanion at physiological pH. Each nucleotide that forms a part of the polynucleotide is a nucleotide residue. The terminal residue whose C5 does not link to another nucleotide is the 5’ end

The terminal residue whose C3 does not link to another nucleotide is the 3’ end

Conventional rule- Always write the Sequence of nucleotide from 5’ to 3’ end

Charecteristics: planar, aromatic, and heterocyclic

Function: key role in metabolic reactions, especially free nucleotides

Adenosine Tri Phosphate (adenine+ribose+triphosphate group) is an important free nucleotide. It is an energy carrier/energy transfer agent.

Photosynthesis or metabolism of carbohydrates or fatty acids gives Adenosine Di Phosphate (ADP)

ATP converts to ADP through hydrolysis

Some nucleotides also act as second messengers. For instance, adenosine 3’,5’-cyclic monophosphate, commonly known as cyclic AMP is a regulatory molecule. 

Derived from: purine or pyrimidine

Purines

Adenine and Guanine

They attach with a five carbon sugar (pentose) through their N9 atoms

Pyrimidines 

Cytosine, Uracil, and Thymine

They attach with a five-carbon (pentose) through their N1 atoms

Adenine, Guanine, and Cytosine occur in both ribonucleotides and deoxynucleotides

Uracil occurs only in Ribonucleotide

Thiamine occurs only in Deoxynucleotide

Purines and pyrimidines can exist in different forms known as tautomers. They readily interconvert to each other and differ only in the position of hydrogen bonds.

Nucleoside

Nucleotides without a phosphate group are nucleosides. 

Nitrogenous Base+ Sugar= Nucleoside

Nucleic acids

DNA 

Structure: As discovered by James Watson and Francis Crick, it forms a double helix. 

Features of Watson and Crick model 

1. Two polynucleotide chains wind around a common axis to form a double helix
2. The two strands are antiparallel, but each forms a right-handed helix
3. The bases are in the core or center of the DNA and the sugar-phosphate chains run along the periphery. This minimizes repulsion between phosphate groups. Two grooves- major and minor make up the helix
4. The bases link to each other through hydrogen bonds.Two hydrogen bonds join Adenine and thiamine and three hydrogen bonds join Guanine and Cytosine. This is complementary base pairing. 

Each of these DNA strands can act as a template for the synthesis of a new strand thereby passing on the hereditary information. 

Chargaff’s rule: According to the rule, “DNA has an equal number of Adenine and Thymine (A=T) and equal number of Guanine and Cytosine (G=C)”

The most common biological form of DNA is B-DNA. In addition, there are confirmations namely, A-DNA and Z-DNA

Let’s look at the features of B-DNA

1. Diameter of the double helix= 20 Å
2. The planes of the nucleotide bases are perpendicular to the helix
3. A near-perfect symmetry of the DNA helix is because each base pair has approximately the same width. This is why they can replace each other in the double helix without distorting the sugar-phosphate backbone eg: A: T can replace T: A and vice versa, G: C can replace C: G and vice versa. But, any other combination of bases like A:G or T:C would severely distort the backbone
4. Each turn can accommodate 10 base pairs (bp)
5. The helical twist is 36 degrees per bp
6. The helix has a pitch of 34 Å

A-DNA

Under dehydrating conditions, B-DNA undergoes a conformational change to A-DNA and this change is reversible. This conformation is wider and flatter with 11.6 bp per turn and a 34 Å pitch. The most striking feature of A-DNA is that the planes of its base pairs at titled at an angle of 20 deg concerning the axis due to which it has a deep major groove and a very shallow minor groove. 

Z-DNA

It has a repeating sequence of CG base pairs and appears as a left-handed helix with 12 bp per turn. With a pitch of 44 Å, a deep minor groove, and no major groove. One can often see this conformation at high salt concentrations

Function of DNA:

1. Carrier of genetic information
   Oswald Avery, Colin MacLeod, and Maclyn McCarty proved this
2. The duplex nature of DNA facilitates replication. When the cell divides, the DNA helix separates into two and each strand acts as a template for the synthesis of a new DNA helix
3. They direct protein synthesis. The genes present in DNA translates to enzymes (most of which are proteins).George Beadle and Edward Tatum proved this and is often known as the one gene-one enzyme hypothesis. The link between DNA and Proteins is RNA
   
   This function of DNA gave rise to the central dogma of molecular biology

Central Dogma of Molecular Biology

DNA—replication———-DNA—transcription——-RNA—Translation——Protein

You will learn the steps in central dogma in an upcoming blog post on replication, transcription, and translation

DNA adopts rather unique structures. Let’s look at them

1. The common type is a palindrome sequence. They are self complimentary and form hairpin or cruciform structures.
2. Three to four strands of DNA pair together to form triplex DNA (with Hoogsteen pairing) and the G tetraplex (with a high concentration of guanosine)

RNA

DNA replication occurs in the nucleus and protein translation occurs in the cytoplasm. So, one component needs to shuttle between the cytoplasm and nucleus and RNA was found to be the ideal candidate.
It is a compactly arranged consisting of a single strand.

Only two differences between DNA and RNA: 1. The deoxyribose in DNA is missing in RNA and 2. RNA has Uracil instead of Thiamine

Sometimes, base pairing within the RNA can give rise to stem-loop structures. Some viruses have a double stranded RNA as their genetic material. However, it synthesizes as a single strand and folds itself into a double-stranded structure due to its complementary nature. The process of transcription always gives rise to a single-stranded RNA.

RNA can be classified into three groups:

Messenger RNA (mRNA)– this carries the genetic information from DNA to the ribosomes. They specify the amino acid sequence in the polypeptide chain. The process of formation of mRNA from DNA is transcription. It is monocistronic if it carries the code for only one polypeptide. It is polycistronic if it carries the code for multiple polypeptides. 

Ribosomal RNA (rRNA)- they are components of the ribosomes. Some rRNA’s also play the role of enzymes as in ribozymes.

Transfer RNA (tRNA)– they play a major role in protein synthesis. 

Chemical properties of Nucleic Acids

Although one might think that DNA and RNA are very flexible. But, this is not the case. Why is it so?

1. The rotation of a base around its glycosidic bond is hindered. Purines have two permissible orientations – syn and anti but only anti- conformation is stable. In all confirmations of DNA, they exist as anti-conformation except for Z-DNA. 
2. The ribose ring exists in two conformations- C2’-endo and C3’-endo. The ring substituents are hidden when the ring is nearly flat. So, the ring puckers and becomes slightly non-planar. The ribose pucker is an important chemical property of nucleic acids. 
3. The sugar-phosphate backbone’s conformation is constrained. But, this is necessary because if the bonds were to rotate freely, the nucleic acid would never be stable. 

Let’s look at the forces keeping these nucleic acids stable

They are stabilized by mainly three forces- Base Pairing, Stacking, and Ionic Interactions

1. Base pairing: it is a glue that holds the double-stranded nucleic acid together. Watson and Crick’s base pairs occur in DNA structures.
   Other hydrogen-bonded base pairs are also known in RNA. 
2. Hydrogen bonds only weakly stabilize nucleic acids
   Adenine and Thymine are bonded by two hydrogen bonds and
   Guanine and Cytosine are bonded by three hydrogen bonds
3. Stacking: they are a result of hydrophobic interactions. They are a form of van-der-waals interaction. Interactions between G and C are greater than A and T. This is why DNA with a high G-C content has a high thermal stability. 

Chemistry of nucleic acids

Both DNA and RNA can be undergo denaturation and renaturation.

DNA is highly viscous at room temperature and neutral pH. However, after 80 degrees C, its viscosity decreases drastically suggesting that DNA has undergone a physical change. 

Just like globular proteins undergo denaturation (as seen in my previous blog)at high temperatures, DNA is also affected by the same. Disrupting the hydrogen bonds between paired bases unwinds the DNA double helix to give two separate strands of DNA. This process does not involve the breaking of covalent bonds. 

Renaturation is a single-step process that happens when the temperature returns to normal. The process is called annealing where the two strands wind around each other to form a double helix/ duplex. However, if they are separated completely, renaturation occurs in two steps. In the first step, the strands find each other through random collisions and form a short segment of complementary double helix. This step is slow. In the next step, the remaining unpaired bases come together as base pairs the the two strands zip themselves up. This step is quick.