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CONTENTS
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NUCLEIC ACIDS
MUTATIONS OF NUCLEIC ACIDS
EXAMPLES OF NUCLEIC ACIDS
COMPONENTS OF NUCLEIC ACIDS
ARTIFICIAL NUCLEIC ACID ANALOGS
BIOLOGICAL FUNCTIONS OF NUCLEIC
ACIDS
REFERENCE
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NUCLEIC ACIDS
Nucleic acids are large macromolecules composed of smaller
nucleotides. These nucleotides are made up of two backbones that alternate
between sugar groups and phosphate molecules (the phosphate makes it slightly
acidic). Extending from both sides of these sugar groups are two nucleotide
bases that bond to each other. These bonding patterns give rise to the double
helix shape that we are familiar with. Nucleic acids are vital for cell
functioning, and therefore for life. There are two types of nucleic acids, DNA
and RNA. Together, they keep track of hereditary information in a cell so that
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the cell can maintain itself, grow, create offspring and perform any specialized
functions it's meant to do. Nucleic acids thus control the information that makes
every cell, and every organism, what it is.
Nucleic acids were discovered by Friedrich Miescher in 1869.
Experimental studies of nucleic acids constitute a major part of modern
biological and medical research, and form a foundation for genome and forensic
science, as well as the biotechnology and pharmaceutical industries.
[The Swiss scientist Friedrich Miescher discovered nucleic acids (DNA) in 1869.
Later, he raises the idea that they could be involved in heredity]
In the 1920's nucleic acids were found to be major components of
chromosomes, small gene-carrying bodies in the nuclei of complex cells.
Elemental analysis of nucleic acids showed the presence of phosphorus, in
addition to the usual C, H, and N & O. Unlike proteins, nucleic acids contained
no sulphur. Complete hydrolysis of chromosomal nucleic acids gave inorganic
phosphate, 2-deoxyribose (a previously unknown sugar) and four different
heterocyclic bases. To reflect the unusual sugar component, chromosomal
nucleic acids are called deoxyribonucleic acids, abbreviated DNA. Analogous
nucleic acids in which the sugar component is ribose are termed ribonucleic
acids, abbreviated RNA. The acidic character of the nucleic acids was attributed
to the phosphoric acid moiety.
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Mutations of Nucleic Acids
While nucleic acids can do so much good for the body, mutation can result
in debilitating or life threatening diseases. There is a long list of genetics
conditions caused by mutations involving nucleic acids. Some of the more
prominent conditions caused by mutations of nucleic acids like DNA and RNA
include:
Diseases of the heart and muscle
Some DNA mutations in mitochondria have been linked to diseases of the
heart and muscles. When there is damage to the mitochondrial DNA, tissues and
organs can begin to deteriorate causing painful and sometimes fatal conditions.
Breast cancer
Mutations of the genes BRCA1 and BRCA2 have been linked to causing
breast cancer. This determination, in the 1990’s, has lead to increased research
regarding these genes and their mutations in an effort to reduce the risk of
acquiring breast cancer.
Ovarian Cancer
The same genes that were determined to cause breast cancer upon mutation
have also been linked to ovarian cancer. Researchers are still working to
determine how these mutations happen and how to prevent them.
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Down Syndrome
Down syndrome is another condition that is caused by a mutation of a gene
in the DNA. In the past several decades, great strides have been made in
medicine in understanding and diagnosing Down syndrome.
Color Blindness
While certainly not as debilitating as some other genetic diseases, color
blindness is also a result of mutation of genes on DNA. This condition is more
prevalent in men and exists when one is unable to distinguish between colors or
to see colors in typical lighting.
Examples of Nucleic Acids
Nucleic acids, best-known as DNA and RNA, are often termed "the
building blocks of life." These building blocks are found in the nuclei of cells
and help proteins to be built, help cells to replicate, govern heredity and the
cell's chemical processes. Nucleic acids are made up of five pieces, or
monomers, including:
Guanine
Cytosine
Thymine
Cytosine
Uracil
These acids are the stores and transmitters of cellular information in the body.
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DNA
Deoxyribonucleic acid is the most common form. Its base pairs are
adenine (A), thymine (T), guanine (G) and cytosine (C). There are small
differences between them. For instance, A and G have a double ring structure,
which allows them to bind to a single ring structure. A binds with T, and G
binds with C. When DNA is replicated, its structure unwinds, splitting the
hydrogen bonds of the bases in half. Complimentary bases are then formed.
This is similar in concept to the way in which DNA is read.
The polymeric structure of DNA may be described in terms of
monomeric units of increasing complexity. In the top shaded box of the
following illustration, the three relatively simple components mentioned earlier
are shown. Below that on the left, formulas for phosphoric acid and a
nucleoside are drawn. Condensation polymerization of these leads to the DNA
formulation outlined above. Finally, a 5'- monophosphate ester, called a
nucleotide may be drawn as a single monomer unit, shown in the shaded box to
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the right. Since a monophosphate ester of this kind is a strong acid (pKa of 1.0),
it will be fully ionized at the usual physiological pH (ca.7.4).
Names for these DNA components are given in the table to the right of
the diagram. Isomeric 3'-monophospate nucleotides are also known, and both
isomers are found in cells. They may be obtained by selective hydrolysis of
DNA through the action of nuclease enzymes. Anhydride-like di- and tri-phosphate
nucleotides have been identified as important energy carriers in
biochemical reactions, the most common being ATP (adenosine 5'-
triphosphate).
RNA
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Another kind of nucleic acid is ribonucleic acid, which is similar in
structure to DNA but instead supplements uracil (U) for thymine. RNA is used
exclusively in viruses and perhaps even the earliest forms of life, but in most
modern life RNA has another critical function. It translates genetic information
to proteins, which help facilitate important functions of the cell.The high
molecular weight nucleic acid, DNA, are found chiefly in the nuclei of complex
cells, known as eukaryotic cells, or in the nucleoid regions of prokaryotic
cells, such as bacteria. It is often associated with proteins that help to pack it in
a usable fashion.
Ribonucleic acid (RNA) functions in converting genetic information from
genes into the amino acid sequences of proteins. The three universal types of
RNA include transfer RNA (tRNA), messenger RNA (mRNA), and ribosomal
RNA (rRNA). Messenger RNA acts to carry genetic sequence information
between DNA and ribosomes, directing protein synthesis. Ribosomal RNA is a
major component of the ribosome, and catalyzes peptide bond formation.
Transfer RNA serves as the carrier molecule for amino acids to be used in
protein synthesis, and is responsible for decoding the mRNA. In addition, many
other classes of RNA are now known.
In contrast, a lower molecular weight, but much more abundant nucleic
acid, RNA, is distributed throughout the cell, most commonly in small
numerous organelles called ribosomes. Three kinds of RNA are identified, the
largest subgroup (85 to 90%) being ribosomal RNA, rRNA, the major
component of ribosomes, together with proteins. The size of rRNA molecules
varies, but is generally less than a thousandth the size of DNA. The other forms
of RNA are messenger RNA, mRNA, and transfer RNA, tRNA. Both have a
more transient existence and are smaller than rRNA.
All these RNA's have similar constitutions, and differ from DNA in two
important respects. As shown in the following diagram, the sugar component of
RNA is ribose, and the pyrimidine base uracil replaces the thymine base of
DNA. The RNA's play a vital role in the transfer of information (transcription)
from the DNA library to the protein factories called ribosomes, and in the
interpretation of that information (translation) for the synthesis of specific
polypeptides.
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Artificial nucleic acid analogs
Artificial nucleic acid analogs have been designed and synthesized by
chemists, and 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.
Nucleic Acid Functions
The human body is made up of millions of cells that work to maintain the
body's overall system and function. Each cell, in turn, has its own set of
processes designed to carry out necessary cell functions. Nucleic acid plays an
essential role in coordinating and maintaining individual cell processes
throughout the body.
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BIOLOGICAL FUNCTIONS OF NUCLEIC ACIDS
1. Replication :
Process by which a single DNA molecule produces two identical copies of
itself is called replication. Replication of DNA is an enzyme catalysed process.
In this process, two strands of DNA helix unwind and each strand serves as a
template or pattern for the synthesis of a new strand. Newly synthesized
complementary strand is an exact copy of the original DNA. In this way
hereditary characteristics are transmitted from one cell to another.
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i) Transcription :
It is the process of synthesis of RNA (mRNA) by using DNA as
template. This process is similar to replication process. Differ in following
ways. In transcription, ribose nucleotide assemble along the uncoiled
template instead of deoxyribose nucleotide and base uracil (U) is substituted
for the base thymine (T). Synthesis of RNA or DNA always takes place in 5'
- 3' direction. Process is catalysed by an enzyme RNA polymerase. In this
way DNA transfers its genetic code to mRNA. After synthesis, RNA
detaches from DNA and moves from nucleus to the cytoplasm where it acts
as template for protein synthesis. DNA returns to its double helix structure.
(ii) Translation :
It is the process of synthesis of protein. This process is directed by
mRNA in the cytoplasm of cell with the help of tRNA (transfer RNA) and
ribosomal particles (RNA – protein complex).The process occurs with the
attachment of mRNA to ribosome particle mRNA then gives the message of
the DNA and dictates the specific amino acid sequence for the synthesis of
protein. 4 bases in mRNA act in the form of triplets and each triplet acts as a
code for a particular amino acid. This triplet is called codon. There may be
more than one codon for same amino acid. E.g. amino acid methionine has
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code AUG while glycine has 4 codons GGU, GGC, GGA, GGG. These
codon expressed in mRNA is read by tRNA carrying anticodon and is
translated into an amino acid sequence. This process is repeated again and
again thus proteins are synthesized. After completion, it is released from
ribosome.
Protein synthesis :
It is a fast process and about 20 amino acids are added in one second. It
may be noted that translation is always unidirectional but transcription can
sometimes be reversed. (RNA is copies into DNA) This is called reverse
transcription (occurs in Retroviruses). Genetic Code Segment of DNA is called
gene and each triplet of nucleotides is called a codon that specifies one amino
acid. This relationship between nucleotide triplets and amino acids is called
genetic code. E.g.
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Reference :
Wolfram Saenger, Principles of Nucleic Acid Structure, 1984,
Springer-Verlag New York Inc.
Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith
Roberts, and Peter Walter Molecular Biology of the Cell, 2007, ISBN
978-0-8153-4105-5. Fourth edition is available online through the
NCBI Bookshelf:
Jeremy M Berg, John L Tymoczko, and Lubert Stryer, Biochemistry
5th edition, 2002, W H Freeman. Available online through the NCBI
Bookshelf: link
Astrid Sigel, Helmut Sigel and Roland K. O. Sigel, ed. (2012).
Interplay between Metal Ions and Nucleic Acids. Metal Ions in Life
Sciences 10. Springer. doi:10.1007/978-94-007-2172-2. ISBN 978-94-
007-2171-5.
Sanger, Frederick. 1980. Determination of Nucleotide Sequences in
DNA.http://nobelprize.org/nobel_prizes/chemistry/laureates/1980/san
ger-lecture.html
