Hello everyone and welcome to this week's blog post. This blog post is the first in a two part series about DNA. In this article, I will explain what DNA is and how it can get damaged. Next week, I will explore some of the consequences of damaged DNA.
What is DNA?
All living organisms need a system to grow and reproduce. This system is achieved through a series of complex mechanisms. DNA is vital for this, as it allows organisms to pass on information to their offspring.
DNA (short for deoxyribonucleic acid) is a polymer, consisting of three smaller components. These components are deoxyribose (a 5 carbons sugar), a phosphate group and nitrogen-containing bases. Alternating sugar molecules and phosphate groups are bound together with phosphodiester bonds - this is where a carbon on each of the molecules is linked with an oxygen molecule.
A nitrogen-containing base is bound to each deoxyribose molecule. There are four different bases that can bind to deoxyribose in DNA - two purine bases (called adenine and guanine) and two pyrimidine bases (called thymine and cytosine).
DNA molecules are made of two separate strands of this polymer - these strands wrap around each other in a double helix, with the nitrogenous bases projecting into the centre. The two strands are arranged so that adenine is always opposite thymine, and cytosine is always opposite guanine. Hydrogen bonds can then form between these bases. This allows the DNA molecule to form a double-helix structure, thus partially protecting it from getting damaged.
In addition, since the hydrogen bonds are individually weak, the DNA molecule can be split into separate strands. This allows the cell to make an identical copy of the DNA molecule during the mitotic cycle. As a result, when the cell divides by mitosis, it can produce an identical copy of the cell. This is very useful as it allows the organism to grow by producing new cells. Mitosis is also essential for asexual reproduction, clonal selection during the immune system's response to an infection, and the replacement of cells in tissues when they get damaged.
DNA is a crucial molecule as it controls the proteins produced by the organism. The structure, and therefore function, of a protein depends on the order and type of amino acids it has. Proteins are produced during translation, which is when mRNA molecules enter ribosomes. There are tRNA molecules inside the cell which have a set of three nitrogenous bases. Each tRNA molecule has a different amino acid attached to it depending on the bases it has.
If a tRNA molecule has the complementary bases to the bases exposed on the mRNA in the ribosome, they form hydrogen bonds with the mRNA. Two tRNA molecules enter the ribosome at the same time, allowing a peptide bond to form between the adjacent tRNA molecules. The tRNA molecules leave the ribosome one at a time, and the mRNA molecule advances, allowing another tRNA molecule to bind and the amino acid chain to grow in length. As such, each set of three bases codes for an amino acid (this set is called a codon).
Since the sequence of bases on the mRNA is a direct result of the sequence of bases on the DNA, this allows the order of bases on the DNA molecule to code for proteins. Consequently, it is very important that the DNA molecule is able to be copied perfectly over and over again, as a single mistake could change the order of bases and thus change the protein produced, which could have devastating effects on the body.
In humans, the genetic material is stored as DNA molecules called chromosomes. We have 46 chromosomes (or 23 pairs of chromosomes). Each chromosome can be divided into sections called 'genes'. A gene is simply a sequence of bases that code for a single polypeptide. Sometimes, these genes can get damaged, so that the sequence of bases changes. In these cases, a different version of the gene is formed - these versions are called alleles.
In eukaryotes, the DNA molecules are wrapped around histone proteins. This allows the genetic material to be much more compact, allowing it to fit inside the nucleus without getting tangled. The histones are able to interact with the DNA as they are basic, allowing them to interact with the acidic DNA. In addition, the histones are also positively charged, while the DNA is negatively charged (due to the phosphate in the sugar-phosphate backbone), which helps the DNA remain untangled.
Furthermore, the DNA molecule also has many regions that do not code for proteins. For example, since the enzymes involved in copying the DNA molecule during replication can't run to the ends of the molecule, DNA is 'capped' with non-coding regions called telomeres. Since these regions don't code for proteins, it doesn't matter if they are not copied to the new molecule exactly. Instead, telomerase enzymes can just 'top up' these regions.
In addition, there are also other non-coding regions found on the DNA molecule. For instance, there are introns located within the parts of the molecule coding for proteins. While these regions are removed before the protein is synthesised, they are very important as they allow regulatory molecules to bind to the molecule. Since the entire genetic code is found in every cell, the body needs a mechanism to switch genes 'on and off'. These regulatory molecules permit the cell to do just that, thus allowing cells to only produce the proteins it needs.
How can DNA be damaged?
Sometimes, the structure in the DNA molecule can be changed, resulting in an altered protein being coded for. This is called a mutation. These mutations can either involve the change in the order of bases (which is known as a gene mutation), or they can involve a change in the structure of a chromosome or the number of chromosomes in the cell.
There are many different ways in which mutations can occur. Mutations can occur randomly in the cell, however, there are many environmental factors which exacerbate the occurrence of these mutations. For example, ionising radiation can damage DNA molecules, as it can cause free radicals to form, which damage the DNA strands.
In addition, UV light can also interact with thymidine (the nucleotide that contains a deoxyribose sugar bound to a thymine base). This causes diamers to form. If these diamers are incorrectly repaired, then mutations occur.
In addition, there are other mutagens which can increase the changes of mutations occurring, including mustard gas and tobacco smoke. As such, coming into contact with these substance increases the chance of getting these mutations and having a defective protein. Additionally, if these mutations affect the proteins responsible for mitosis, then cancerous tumours can form.
In gene mutations, the order of bases is changed. Sometimes this does not have an impact on the protein that is coded for - if this occurs, then the mutation is called a 'silent mutation'. Silent mutations occur because the DNA code is denegerate. This means that an amino acid can be coded for by many different sets of 3 bases, so a change in a single base does not always have an affect on amino acid coded for.
In addition, a single base change can also cause codon to be changed into a stop codon. This essentially causes only part of the protein to be produced, which can have disastrous effects. Furthermore, frameshift mutations can also occur. This is where one or multiple bases are added or removed. If the number of bases added or removed is not a multiple of three, then this can cause the entire sequence of bases to be shifted, thus changing all of the codons.
Meanwhile, in chromosome mutations, sometimes part of all of a chromosome is incorrectly copied during meiosis. This results in one of the gamates having an extra set of genes, or too few genes, which can cause disease in the offspring.
I hope you enjoyed this week's article! Next week, I will explain some of the consequences of damaged DNA, including the production of new alleles (and the resulting effect on natural selection) and some of the diseases associated with damaged DNA.
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