DNA: Nature and Structure of DNA | Nucleic Acid

The below mentioned article provides a study note on DNA.

Nature of DNA:

DNA is a very long polymer of purine and pyrimidine mononucleotide monomers bound one to the other by phosphodiester bridges. It exists as a double-stranded molecule in nature. The strands are held together by Vander Waals’ forces and the purine and pyrimidine bases of the two strands are held together by hydrogen bonding.

The two strands extend in opposite direc­tion, i.e., each is antiparallel. Each purine or pyrimidine base in one strand is related to pyrimidine or purine base of the other strand i.e., Adenine (A) is paired with Thymine (T) and Guanine (G) is paired with Cytosine (C).

Genetic information is contained in the sequence of mononucleotide of the DNA molecule. For each gene in the DNA mol­ecule, there is a “sense” strand and its com­plementary “antisense” strand.

Watson and Crick double-stranded model of DNA strongly suggests the replication of DNA molecule in a semiconservative manner. When each strand of the double- stranded DNA molecule separates during replication, each can then serve as a tem­plate on which a new complementary strand can be synthesized.

Each of the 2 newly formed double- stranded DNA molecule contains one strand (but complementary) from the par­ent double-stranded DNA molecule. The two newly formed double-stranded DNA molecule can then be sorted between 2 daughter cells. Each daughter cell will contain DNA molecules with information identical to that which the parent pos­sesses.

The double-stranded structure of DNA and the template function of each old strand on which a new complementary strand synthesized and also the semiconservative and conservative repli­cation are given in Fig. 25.2.

Histones are the most Abundant Chromatin Proteins:

1. The histones are the small family of closely related basic proteins. HI histones are the least tightly bound to chromatin and are easily removed with a salt solu­tion, after which chromatin becomes solu­ble.

2. The core nucleosomes contain four classes of histones: H2A, H2B, H3, and H4. The slightly lysine — rich histones are H2A and H2B, whereas the arginine — rich histones are H3 and H4.

3. Four core histones are subject to five types of covalent modifications acetylation, methylation, phosphorylation, ADP- ribosylation, and covalent linkage (H2A only).

4. The histones interact with each other in very specific ways. H3 and H4 form a tetramer, while H2A and H2B form dimers. Two of these histone tetramers associate to form the histone octamer.

Some Regions of Chromatin are ‘Active’ and others are ‘Inactive’:

1. Chromatin containing active genes differs in several ways from that of non-active re­gions. The nucleosome structure of active chromatin is absent in highly active re­gions. DNA in active chromatin contains large regions (about 100,000 bases long) that are sensitive to digestion by a nucle­ase such as DNase 1.

2. DNase 1 will digest DNA not protected by protein into deoxynucleotides. The sen­sitivity to DNase 1 of chromatin regions reflects only a potential for transcription.

3. There exists shorter stretches of 100-300 nucleotides that exhibit an even greater sensitivity to DNase 1 within the large re­gions of active chromatin. In many cases, if a gene is capable of being transcribed, it must have a DNase hypersensitive site in the chromatin.

4. Transcriptionally inactive chromatin is densely packed during interphase and isreferred to as heterochromatin. Transcrip­tionally active chromatin stains less densely and is referred to as euchromatin. Generally, euchromatin is replicated ear­lier in the mammalian cell cycle than is heterochromatin.

5. Heterochromatins are of two types — con­stitutive heterochromatin and facultative heterochromatin. Constitutive hetero­chromatin is always condensed and inac­tive. It is found in the regions near the chromosomal centromere and at chromo­somal ends (telomeres). Facultative het­erochromatin is at times condensed but at other times it is actively transcribed and appears as euchromatin.

DNA is Organized into Chromosomes:

1. At metaphase, mammalian chromosomes possess a two-fold symmetry with identi­cal sister chromatids connected at a cen­tromere.

2. The centromere is an A—T region of about 130bp. It binds several proteins with high affinity. This complex, called the kinetochore, provides the anchor for the mitotic spindle.

3. The ends of each chromosome contain structure called telomeres. These consist of short, repeat TG-rich sequences. Human telomeres have a number of repeats of the sequence 5′-TTAGGG-3′, which can ex­tend for several kilo-bases.

4. Telomerase is the enzyme responsible for telomere synthesis and maintains the length of the telomere. Since telomere shortening is associated with malignant transformation (and aging), telomerase has become an attractive target for cancer chemotherapy.

5. Each of the 23 chromatids in the human haploid genome contains averagely 1.3 x 10⁸ nucleotides in one double-stranded DNA molecule. The length of each DNA molecule must be compressed about 8000-fold to generate the structure of a con­densed metaphase chromosome.

Chromosomal Recombination is One Way of Rearranging Genetic Material:

1. Genetic information can be exchanged be­tween similar or homologous chromo­somes. The exchange or recombination event occurs during meiosis in mamma­lian cells and requires homologous chromosomes.

2. A process of crossing over results in an equal and reciprocal exchange of genetic information between homologous chro­mosomes. If the homologous chromo­somes possess different alleles of the same genes, the cross-over may produce remark­able and heritable genetic linkage differ­ences.

3. In rare cases, if the alignment of recombi­nation event may result in an unequal ex­change of information.