The Role of Mutagenic Agents in DNA Modification
Classification of DNA modification associated Agents
Mutagenic agents are those chemical and/or physical substances that can modify DNA at nucleotides level. Those agents that modified DNA are divided into “Endogenous” and “Exogenous” groups.
Detail study about different types of mutations, see the following post, “Why understanding mutations phenomena is mandatory for the application of Protein Engineering?”
Endogenous Agents
Endogenous agents are normally biological molecules that are naturally present in the cells and involve in different cellular activities. In Endogenous DNA damage, DNA sequence can be modified naturally, when there is some disturbance in internal cellular mechanisms. For example;
- DNA can be modified during Replication by Polymerase enzyme to incorporate wrong nucleotide.
- May be due to unequal crossing over during recombination errors.
- Sometimes, N bases in the DNA become deaminated and or depurinated, that result into wrong base pair in ds DNA.
- Reactive oxygen species that are produced as a byproduct can change DNA normal sequence. All these processes occur within the cell of an organism.
Exogenous DNA Damaging Agents
In case of Exogenous DNA damage, different types of exogenous agents have been discovered that modified DNA either specifically or non-specifically when DNA is exposed to these agents. These agents are further divided into two major groups. Chemical and physical agent.
Chemical Mutagenic Agents
Chemical agents may be natural chemical such as aflatoxin present in the foods, or may be man-made chemical such as Nitrogen Mustard, that was used as a chemical weapon in World War 1 (abbreviated as WW1). Another example of man-made chemical that involve in DNA modification is benzopyrene. Benzopyrene is particularly, present in smoke of substances such as coal, auto and cigs.
Physical Mutagenic Agents
In addition, DNA can also be modified by applying either some physical agents for example UV radiation from sunlight or ionizing radiation.
- Ionizing radiation are also two types.
- Natural ionizing radiation may be natural gas such as radon gas.
- Ionizing radiation may be man-made such as from X-rays or some nuclear Tests. In Protein Engineering, we also apply exogenous sources to modify DNA in order to achieve protein with new desired properties.
- Similarly, another nucleotide analog N4-hydroxycytidine was used in later 1974, in the lab of Charles Weissmann. Incorporation of N4-hydroxycytidine successfully made transition mutation by changing GC base pair into AT.
- For example, there is a short sequence of DNA that is AGCTT. In this sequence normal cytosine is changed into N4-hydroxycitidine. When this modified sequence of DNA is replicated, the new synthesized strand of DNA come with A instead of G. In the next replication phase. The new synthesized strand of TCAAA, will be AGTTT. Hence, in this way GC pair is completely replaced with AT.
Objective of DNA modification
Modified DNA are transcribed with altered codon which are translated by ribosome to incorporate our desired amino acids. Later we can test different properties of the new protein that is modified at amino acids level. Among these different strategies that are used to modified proteins. Hence These agents can be used in Protein Engineering for DNA modification.
Now we have some ideas about how to modify DNA bps sequences, using some suitable mutagen.
