Question

What types of agents can induce changes in the DNA sequence and what are typical changes observed with each? How are these changes repaired?

Answer 1

Answer: Changes in DNA sequences can be random or induced. Random change occur due to sudden mutation or depending on usage of gene over a long period of time (also studied as evolution). However, an artifical change/alteration in DNA sequence (reversible or irreversible) can be done by:

1) Radiation: Ionising/non-ionising radiation causes DNA breakage, dimerisation or other severe damages. For instance,

(a) Ultra-violet radiation (UV rays) is a non-ionising radiation that induces dimerisation of adjacent Thymine residues on a DNA molecule. This change in DNA sequence is irreversible.

(b) High dose Gamma rays break the DNA molecules that can be repaired by cell during replication. Severe damage include breakage of chromatin arm or formation of rings, which cannot be rectified.

(c) Cesium-137, Cobalt-60 and X-rays cause breakage in double helicle structure of DNA molecule. When DNA molecule is exposed to high dosage of the ionising radiation, they cause irreversible damage to the DNA molecule.  

2) Biological: Recombinant DNA technology is used to insert/delete a foreign DNA into the genome of an organism. Insertion/deletion of a DNA sequence changes the sequence of original DNA molecule. The processes used are: transformation, Transfection, Transposition etc.

Changes observed are: Addition/deletion of DNA sequence, duplication, frameshift (if addition or deletion occurs in Open Reading Frame (ORF) of a gene).

This could be reversible if the DNA sequence is inserted to or deleted from from a known location on given DNA sample i.e., genome. Known sequence whether deleted or inserted can be again reverted to get the original DNA sequence. But, if an unknown DNA sequence is inserted or deleted randomly in to a genome, then the change is irreversible, It cannot be reverted.

3) Chemical: There are a number are chemical agents that alters the DNA sequence. They are:

(a) Nitrous acid causes modification of DNA sequence. The modifications caused are irreversible. for instance, it reacts with amino groups of nitrogen bases. Adenine is deaminated to hypoxanthine, cytosine into uracil, and guanine into xanthine. Therefore, nitrous acid causes base transition i.e., A-T ? G-C transitions.

(b) Acridines dye intercalates between the double helix structure of DNA and causes insertion or deletion of one or two bases, due to which it leads to change in reading frame, also known as Frameshift mutation. This change is irreversible.

(c) Proflavins binds to DNA, intercalates into it and inhibits DNA replication.

(d) Base analogues substitution will result in altered base pairings that lead to structural changes in DNA and affect DNA replication and transcription of genes. This can be reversed by replacing the base analogues with original bases for next few DNA replication cycles.

(e) ethyl methane sulfonate (EMS) causes  Guanine to 6-ethyl Guanine formation which pairs with Thymine. This danage is irreversible.

(f) methyl methane sulfonate (MMS) methylates DNA that stalls DNA replication. In some cases, it also causes DNA breakage. This can be reversed by enzyme that removes methyl group, present inside the cell. It demethylate the DNA sequence ans restore the original DNA sequence.

(g) Diethylsulfate (DES) is a very strong alkylating agent. it ethylates O⁶ of Guanine. It is irreversible.