Nucleic Acid

Nucleic acid is a macro molecule composed of chains of nonnumeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acid. Nucleic acids are universal in living things, as they are found in all cells and viruses. Nucleic acids were first discovered by Friedrich Miescher in 1871.Artificial nucleic acids include peptide nucleic acid, Morpholino and locked nucleic acid as well as glycol nucleic acid and threose nucleic acid. Each of these is distinguished from naturally-occurring DNA or RNA by changes to the backbone of the molecule

Types of nucleic acids: - 1.Ribonucleic acid
2. Deoxyribonucleic acid

Nucleic acid components: - 1 .Nucleo bases
2. Nucleosides
3 .Nucleotides and deoxy nucleotides.

Stranded DNA viruses

Some small viruses carry their genome as single-stranded DNA (ssDNA) molecules. These viruses have a simple genome, one gene for a viral nucleocapsid protein and another gene for a DNA replication enzyme. The virus with a ssDNA genome also faces a serious replication problem in the host cell. When introduced into cells these genomes can not be used to make viral proteins because the only template for transcription is double stranded DNA

For this reason the first step after infection is the conversion of the viral ssDNA into dsDNA using host cell DNA polymerase. You may recall that DNA polymerase requires a primer for replication. In some of these viruses the 3 end of the viral DNA folds back and forms dsDNA by base pairing with an internal sequence. In this way, the primer is built into the genome and the 3 end can be extended to create dsDNA that serves as a template for transcription. The resulting transcripts are translated to make the viral proteins the replicated viral DNA is converted back into a ssDNA genome, and the virion is packaged for export. Canine and feline parvo viruses are members of the ssDNA virus family.

Mitochondrial DNA Damage

In human cells, and eukaryotic cells in general, DNA is found in two cellular locations inside the nucleus and inside the mitochondria. Nuclear DNA (nDNA) exists as chromatin during non replicative stages of the cell cycle and is condensed into aggregate structures known as chromosomes during cell division. In either state the DNA is highly compacted and wound up around bead-like proteins called histones. Whenever a cell needs to express the genetic information encoded in its nDNA the required chromosomal region is unravelled, genes located therein are expressed, and then the region is condensed back to its resting conformation. Mitochondrial DNA (mtDNA) is located inside mitochondria organelles, exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. Inside mitochondria, reactive oxygen species (ROS), or free radicals, byproducts of the constant production of adenosine triphosphate (ATP) via oxidative phosphorylation, create a highly oxidative environment that is known to damage mtDNA. A critical enzyme in counteracting the toxicity of these species is superoxide dismutase, which is present in both the mitochondria and cytoplasm of eukaryotic cells.

DNA TESTING

There have been two main types of forensic DNA testing. They are often called RFLP and PCR based testing, although these terms are not very descriptive. Generally, RFLP testing requires larger amounts of DNA and the DNA must be underrated. Crime-scene evidence that is old or that is present in small amounts is often unsuitable for RFLP testing. Warm moist conditions may accelerate DNA degradation rendering it unsuitable for RFLP in a relatively short period of time

PCR-based testing often requires less DNA than RFLP testing and the DNA may be partially degraded, more so than is the case with RFLP. However, PCR still has sample size and degradation limitations that sometimes may be under appreciated. PCR-based tests are also extremely sensitive to contaminating DNA at the crime scene and within the test laboratory. During PCR, contaminants may be amplified up to a billion times their original concentration. Contamination can influence PCR results, particularly in the absence of proper handling techniques and proper controls for contamination.PCR are less direct and somewhat more prone to error than RFLP. However, PCR has tended to replace RFLP in forensic testing primarily because PCR based tests are faster and more sensitive.

DNA Damage and Mutation

It is important to distinguish between DNA damage and mutation, the two major types of error in DNA. DNA damages and mutation are fundamentally different. Damages are physical abnormalities in the DNA, such as single and double strand breaks, 8-hydroxydeoxyguanosine residues and polycyclic aromatic hydrocarbon adducts. DNA damages can be recognized by enzymes, and thus they can be correctly repaired if redundant information, such as the undamaged sequence in the complementary DNA strand or in a homologous chromosome, is available for copying. If a cell retains DNA damage, transcription of a gene can be prevented and thus translation into a protein will also be blocked. Replication may also be blocked and/or the cell may die

In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and these errors are a major source of mutation

Given these properties of DNA damage and mutation, it can be seen that DNA damages are a special problem in non-dividing or slowly dividing cells, where unprepared damages will tend to accumulate over time. On the other hand, in rapidly dividing cells, unprepared DNA damages that do not kill the cell by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell’s survival. Thus, in a population of cells comprising a tissue with replicating cells, mutant cells will tend to be lost. However infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism, because such mutant cells can give rise to cancer. Thus DNA damages in frequently dividing cells, because they give rise to mutations, are a prominent cause of cancer. In contrast, DNA damages in infrequently dividing cells are likely a prominent cause of aging.