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Friday, February 22, 2019

Chemistry of Biomolecules Essay

Our split up on desoxyribonucleic acid is divided into 3 parts (I) Genetics (II) desoxyribonucleic acid structure (III) Concepts and applications.I. Genetics In the primordial period, simple molecules were organise from atoms and from these molecules, macromolecules were ricocheted. These macromolecules formed life and all living beings. The classical comp whiznttic and heredity observations in the 19th century started the search for the bank line of life.The transforming principle of desoxyribonucleic acid was present from the experiment in which non-pathogenic (R-form) and virulent (S-form) but heat treated bacteria, when co-injected, could massacre the mice. After that, the link in the midst of genes ( deoxyribonucleic acid) and genotype / phenotype was established. The link between the features of an organism and genes was established.II. desoxyribonucleic acid structure The genomic desoxyribonucleic acid of a eukaryotic jail mobile phone is situated in a special or ganelle, the substance, whereas in a prokaryotic cell in that respect is no nucleus. In a virus, including bacteriohage, the genome is packed efficiently. The nucleus of a gracious cell contains complete genetic deoxyribonucleic acid, organized in 46 chromosomes (22 autosomal pairs and twain sex chromosomes). Chromatid is one of the two identical copies of deoxyribonucleic acid in a chromosome. The two copies approach each other at the centromere. The ends of desoxyribonucleic acid in a chromosome be called telomere. The location of a gene in a chromosome is marked as, say, 7q31.2 where 7 refers to the chromosome number, q is the long arm (the in short arm of the chromosome is called p), 3 refers to the shargon of a chromosome when colored victimisation a particular process, 1 refers to band 1 in that region and 2 refers to a sub-band within band 1.In the chromatin, deoxyribonucleic acid is appal around the histone core ( do by 2 copies each of the H2A, H2B, H3 and H4 pr oteins) and clamped by the H1 protein. Anytime this DNA is accessed for some(prenominal) biochemical reaction, there allow be physical rearrangement of DNA and the histone core and furthermore the histone proteins undergo chemical modifications, like acetylation and methylation.Two strands of DNA form duplex DNA by base-pairing. In a basepair, the two bases are unlikely to be perfectly aligned or coplanar. In the same token, two adjacent basepairs also need not be perfectly parallel to each other. on that point are three forms of DNA B-DNA, A-DNA and Z-DNA. The B form is the physiological form. The other two forms are synthetic from specific sequences. While the first two forms are right pass helices, the last one is left-handed. In the B-form, the minor groove is narrow and the major groove is wide whereas in the A and Z forms, the groove widths are nearly the same. Also, a basepair in the B-form tracks the helical axis whereas in the A-form, a basepair is very(prenominal) m uch away from the helical axis. However, in the Z-form a basepair lies in-between.Supercoiled DNA In a chromosome (or even in a circular plasmid), DNA exists in a supercoiled form. Several studies have established the connection between the number of base-pairs (linking number, twist) and the level of supercoiling (writhing number). Assume there are 260 B-DNA base-pairs (10 base-pairs will form one full turn, Fig. 1 start from base-pair 1 on a strand and come to the same but one earlier billet on the same strand after 10 base-pairs the next 10 base-pairs form the next one round and so on).Now, convert the elongated DNA into circular DNA by connecting the ends of the same strands. The twist T = total base-pairs / 10 = 260/10 = 26. The linking number is the number of times one strand crosses the other, which is also 26. So the equation becomes,L = T + W or 26 = 26 + 0Now cut scarce if one strand and unwind that strand two times and reconnect the ends. That means, L becomes 24. In order to balance the above equation, 24 = 26 2 or W becomes -2. Or, the new circular adjusts (writhes) with two cross-overs. If you over-wind by two, L = 28 and W = +2. Even now, the circular DNA writhes by 2 but in the opposite direction.Apart from DNA, ribonucleic acids are also very grievous in several(prenominal) cellular processes. There are 3 types of RNA, mRNA, rRNA and tRNA. Of these 3 classes, the tRNA is normally depicted in the clover flip form, displaying its amino group acid acceptor region and the anti-codon region. An amino-acyl tRNA synthetase enzyme attaches a corresponding amino acid to the tRNA. An important and emerging field is non-coding RNA.Class 1bIII. Applications and concepts There are several applications and processes that involve nucleic acids. However, due to the limitation of time, we will learn whole a few applications.1. DNA return key In molecular biology, the important fundamental processes are the cell cycle (including DNA replication the fashioning of DNA exploitation a DNA path fall outer), organization (the devising of mRNA apply a DNA template) and translation (the making of a protein employ mRNA as a template). The next level of events includes reverse transcription (the making of DNA using an RNA template) and the making of RNA using an RNA template. The making of a protein using a DNA template is not yet known.In prokaryotic DNA replication, DNA is unwound by enzymes like helicases and long leading strands ( for the parental 3 to 5 strand) and several short lagging strands (for the parental 5 to 3 strand) are made by the DNA polymerase. The short fragments are joined by ligases. If there is each problem during DNA synthesis, like base-pair mismatch, selected enzymes fix those problems.In a eukaryotic cell, there are several origins of DNA replication (dedicated sequences in DNA) in a chromosome. DNA replication must be initiated only once per origin per cell cycle. First, origin replication protein co mplex (ORC) binds to the origin of replication. The CDC6 protein (CDC28 in yeast) binds to ORC. The CDT1 protein binds to CDC6. Next, the mini chromosome maintenance proteins 2 to 7 (MCM 2-7) binds to the above proteins. The gathering of all these proteins is called licensing and the above complex of all these proteins is called the pre replication complex (pre-RC).There are two systems by which DNA re-replication is prevented. The first mode is through with(predicate) the involvement of cyclin dependent kinases (CDKs). We are not going to review that mode here. The other mode is through the involvement of geminin, a protein.Once DNA replication is initiated, Geminin binds to Cdt1 and primes it for degradation. Once Cdt1 is removed from the pre-RC, there cannot be another DNA replication firing. At the end of the cell cycle, even geminin is degraded. This way, DNA replication takes place only once per cell cycle. We have published the structure of geminin. The geminin-Cdt1 comple x structure is also published by another group.2. clone In conventional sexual reproduction or in vitro fecundation (IVF), an egg is impregnated by a sperm cell. But in cloning, the nucleus of an egg is removed and a nucleus from any suitable cell from an individual is implanted. This cell grows with the same genetic make-up of the nucleus giver (not the egg donor).3. DNA microarray This development is an important tool to study how a normal cell and an affected cell (say, a cancer cell) guide and what are the genes that are up-regulated and down-regulated. On a commercial DNA chip, rummy and short wiz stranded DNA fragments of all known human genes (as of today) are immobilized on glass. Take a normal cell and a cancer cell. Make complementary DNA for all the RNAs in the cells. cover the normal cell DNA with a dye (say green) and that of the cancer cell with a red dye. Now pass the two pools of DNA through the chip. The genes that areactive only in the normal cell (thereby ma king mRNA and hence cDNA) will bind to their complementary fragments (immobilized on the chip) and will cast green signal when detected. Similarly, the genes that are active only in the cancer cell will bind to their complementary fragments and will emit red signal. The genes that are common to both cells will give fall out yellow signal. From this we can learn which genes are upregulated and down regulated in a particular cell for a particular disease condition.4. Transgenic / reporter genes Selected color displaying proteins, like green fluorescent protein (GFP), can be utilise as reporters to identify the location of protein expression for a protein of interest. The GFP gene is wedded to the gene of our interest and injected in an embryo and the location of protein expression is visually observed. Such techniques can be used to generate multicolored ornamental fish for the same species.5. DNA protein interaction Several proteins interact with DNA. For example, transcription factors bind to the promoter / enhancer regions of a gene. Restriction enzymes bind to and cut DNA. DNA polymerase is involved in DNA replication and RNA polymerase is important for transcription. Furthermore, amino-acyl tRNA synthetases bind to tRNAs and attach corresponding amino acids to them.6. RNA impediment Most of the free forms of RNA, messenger RNA molecules in particular, are single strands. tRNAs and selected RNA regions are double-stranded. Many viruses, however, form long stretches of double-stranded RNA when they replicate.When our cells find double-stranded RNA, it is often a sign of an infection. However, plant and animal cells have a more targeted defense that attacks the viral double stranded RNA directly, termed RNA interference.Viral double-stranded RNA are cut into pieces (about 21 base-pairs), called small busybodied RNA (SiRNA) by the protein Dicer. The argonaute protein strips away one strand from the siRNA, and then looks for any viral messenger RNA that m atches it. If it finds some, it cleaves the RNA, destroying it. In this way, the cell removes all viral messenger RNA that is the same as the original double-stranded piece prime and processed by dicer.Based on this principle, we can synthesize a non-natural interfering RNA, then insert it into a cell to destroy any messenger RNA that we desire. Researchers use these small RNA molecules to fight disease, for instance, using them to knock out cancer genes.7. RNA modifying enzymes RNA has to be circumscribed in selected cellular processes. For example, uridine is modified to pseudo-uridine by pseudo-uridine synthase enzymes.

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