Types of DNA

                                  Types of  DNA

Introduction

We all are the spectacular splendid ( fine, grand, superb, impressive, marvelous, wonderful, fabulous , super) manifestation  (expression, demonstration) of life

We all have languages ,we all have affection and we all have gene, and gene is made of DNA which is the ultimate language of life for evolution, existence and enhancement.

Let us interact with it in some more closer manner today…

Griffith’s Experiment

In the late 1920s, Frederick Griffith studied transformation process in Pneumococcus and gave the concept of Transforming agent

In 1940s Avery, Macleod and Mac Carty with treatment of DNase, RNase and protease proved that Transforming agent is DNA

Hershy and Chase experiment

        A second experimental approach indicating that DNA is the genetic material for Bacteriophage also came from the study of Hershy and Chase

Watson and Crick

The crystallography work of Franklin and Wilkins suggested a helical structure with two strands, with 10 base pair per turn

The work of Chargaff indicated that the amount of A equals T and the amount of G equals C

Finally in 1962 on the basis of all pieces of information Watson and Crick suggested the Double Helix structure of DNA for which they were awarded with Noble prize in 1962

Key features of DNA structure

 DNA is a right handed double helix

The bases in opposite strands Hydrogen bond according to the A-T and G-C  rule

The two stands are anti parallel with regards to their 5’ to 3’ directionality

There are approx. 10 nucleotides in each strand per complete 3600 turn of the helix

Nucleotides are linked by phosphodiester linkage, It has been estimated that half life for hydrolysis by phosphodiester linkage in DNA is about 200 million years.

A-DNA

A-DNA structure is shorter and thicker

Found under condition of low humidity and high salt concentration

There about 11 base pairs per helical turn with vertical rise of 2.56 Å per residue

Very deep major groove and shallow minor grooves are created

Displacement of the axis also forms a whole approx. 3 Å in diameter

B-DNA

The average overall structure of DNA in living organisms is believed to be B-DNA like. Notably this conformation unlike the A and Z forms is highly flexible

Found under condition of high humidity and low salt concentration and was the basis of Watson-Crick structure

The helix is relatively long and thin with approx. 10 base pairs per helical turn. The rise per residues is 3.4 Å, the approx. thickness of bases

The base pairs are nearly perpendicular to the helical axis

The major and minor grooves are roughly the same s

Z-DNA

It incorporates a left handed helix rather than the usual right handed variety with zigzagging backbone

The Z-DNA structure is longer and much thinner than that of B-DNA and completes one turn in 12 base pairs

The major grooves are not distinct and minor grooves very deep

The biological function of Z- DNA is not known. Some evidences exist that suggest that Z-DNA influences gene expression and regulation

Bent DNA

DNA sequences with runs of 4 to 6 adenine phased by 10 bp spacers produced bent conformation

DNA bending appears to be a fundamental element in interaction between DNA sequences and proteins that catalyze central processes, such as replication, transcription and site specific recombination

Bending also occurs because of photochemical damage or miss pairing of bases and serves as a recognition signal for initiation of DNA repair

Anti-tumor antibiotics & DNA

The best studied example is the antitumor drug Cisplatin, a tetra coordinate platinum complex

Cisplatin is used alone or in combination with other antitumor agents to treat variety of tumors including  testicular, ovarian, bone and lung cancer

Hairpins and Cruciform DNA

Double hair pins often called cruciform structures can be found in some DNA sequences. A special kind of sequences referred as a palindrome is required

The word palindrome is of literacy origin and usually refers to a statement that reads the same backward and forward

The overall biological function for cruciform is only circumstantial and has not been established

Hoogsteen triple helix
and H- DNA

Triple stranded DNA ( H- DNA)

Normal Watson-Crick pairing is A-T and G-C but later it was discovered that de-oxy triplets like T-A-T and C+- G-C can also be formed which is known as Hoogsteen type base-pairing

H-DNA may play a role in control of Transcription, Replication and Recombination.

Hereditary persistence of fetal hemoglobin

Hereditary persistence of fetal hemoglobin (HPFH) is a group of conditions in which fetal hemoglobin synthesis is not turned off with but continues into adulthood

The disease results from failure in control of transcription from human Gγ- and Aγ globulin genes. Affected chromosome fails to switch from γ to β chain synthesis

Four stranded DNA

Guanine nucleotides and highly G rich nucleotides from novel tetramer structures called G quartets

Four stranded structures are stabilized by the presence of metal cations specially sodium and potassium

X-ray diffraction and NMR experiment have shown that C-rich oligodeoxyribonucleotide can form a  complementary novel type of four stranded complex called i-DNA

Importance of four stranded DNA

Telomerase activity  has been detected in most tumor cell lines and may be responsible for  cancer

A new approach towards cancer treatment is immerged as telomerase inhibition which involves use of the drug that binds with G- quadruplex DNA

 Large aromatic molecules such as porphyrins and antraquinones selectively binds and stabilize G- quadruplex DNA structure

Slipped DNA

DNA regions with direct repeats symmetry can form structures known as slipped, miss paired DNA (SMP-DNA)

Although SMP-DNA has not yet been identified in vivo, genetic evidences suggests that this type of DNA has undoubtedly involved in spontaneous frame shift mutagenesis

Duplication of certain simple triplet repeats that are implicated as the basis of several human genetic diseases may also occur by this mechanism like fragile X syndrome.

Restriction Fragment Length Polymorphism (RFLP)

Restriction enzyme digest of homologous chromosomes contain fragments with different length which can be used to compare the homology in DNA

RFLP is particular valuable for diagnosing inherited diseased for which the molecular defect is unknown

DNA sequencing by di-deoxy method

DNA is to be incubated with DNA polymerase I, primer and the four ddNTP substrates

When the di deoxy analog is incorporated into the growing polynucleotide in the place of normal; nucleotide chain growth is terminated

And a series of trumpted chain is generated which after electrophoratic analysis gives the sequence of DNA

PCR

In 1984, Karry Mullis devised a method called the polymerase chain reaction (PCR) for amplifying specific DNA sequences in vitro condition

The main steps involves separation of DS DNA, binding of primer, elongation and again separation and repetition of the same.

Chemical Synthesis Of  DNA

In the first step the DMTR group is cleaved off

In second step next monomer is added in protonated form

Finally to stabilise the product the trivalent phosphorous is oxidised to the pentavalent state, forming a phosphodiester bond.

Bio-chips

Bio-chip is an emerging technology is based on the hybridization potential of DNA which is used for comparing the DNA sequences and even expression analysis

Bio-chip technology is used for genetic diagnostics, drug discovery, and basic research applications

Genomics

Gene Bank

EMBL nucleotide sequence database

Adleman DNA computer experiment

Adelman  devised a way of applying DNA manipulation techniques to the "Hamilton Path Problem" - for several cities by using Strands of DNA represent the seven cities

These molecules are then mixed in a test tube

Within a few seconds, all of the possible combinations of DNA strands, which represent answers, are created in the test tube

The success of the Adleman DNA computer proves that DNA can be used to calculate complex mathematical problems

Advantages of DNA computer

More than 10 trillion DNA molecules can fit into an area no larger than 1 cubic centimeter (0.06 cubic inches). With this small amount of DNA, a computer would be able to hold 10 terabytes of data, and perform 10 trillion calculations at a time so  that it will make computers smaller than any traditional computer

DNA computers can perform calculations parallel to other calculations

Besides the traditional use, computers may also lead us to a better understanding of a more complex computer -- the human brain

Conclusion

A striking characteristic of DNA is its ability to encode an enormous quantity of biological information. For example, human cell contain information for the synthesis of about 50,000 to 1, 00,000 proteins

This information is stored in the cell nucleus, a package roughly 0.00001 meter in diameter. Despite this compactness, information in DNA is readily accessed and duplicated on command

The ability to store large amount of information on molecules and to access it readily is still far beyond modern information technology

The capacity of nucleic acid to maintain and transmit the archived information efficiently arises directly from their chemical structure

Thus DNA seems to be not only and self replicating but also in the knowledge of recent development may become self analysing and problem solving ultimate mechanism in future.