Wednesday, September 12, 2018

Write the mode of action of following mutagens:

5-BU:

The pyrimidine 5-bromo-uracil is a thymine analog, the bromine at the 5- position being similar in several aspects to the methyl group at the 5-position in thymine. The presence of the bromine, however, changes the charge distribution and increases the probability of tautomeric shifts. In its more stable keto form, 5-BU pairs with adenine. After a tautomeric shift to its enol form, 5-BU pairs with guanine. After one round of replication, an AT-GC transition occurs. The presence of 5-BU also increases the sensitivity of the DNA to UV which itself is mutagenic.

EMS:

Compounds that transfer alkyl groups (CH3-, CH3CH2) to the amino or keto groups of the nucleotides are called alkylating agents. For e.g., Ethyl methane sulfonate (EMS) is a chemical mutagen, which alkylates the keto-group in the 6-position of guanine and forms the abnormal base O6-ethylguanine. During replication, DNA Pol. that catalyzes the process, frequently place thymine instead of cytosine, opposite O6-ethylguanine. Following subsequent rounds of replication, the original base pair G:C can become an A:T pair (a transition mutation).

Acridine Orange:

Intercalating agents such as acridine orange have dimensions that allow them to wedge between the stacked base pairs in DNA. In so doing, they increase the rigidity and alter the conformation of the double helix, possibly causing slight "kinks" in the molecules or they can distort a DNA strands to unwind. These changes in DNA structure can affect many functions involving replication, transcription and repair. In many cases, when DNA molecules containing intercalated acridines replicate, additions and deletions of from one to a few base pair occurs. These small additions and deletions, usually of a single base pair result in reading frameshifts for the portion of the gene distal to the mutation.

UV:

UV radiations are readily absorbed by certain substances such as purines and pyrimidines, which then enter a more reactive or excited state. The maximum absorption of UV by DNA is at a wavelength of 254 nm. Because of their lower energy, they penetrate tissues only slightly, usually only the surface of multicellular organisms. However, it is a potent mutagen for unicellular. The two major product of UV absorption by pyrimidines appear to be pyrimidine hydrates or dimers. Thymine dimers appear to cause mutations  indirectly in two ways: (a) Dimers apparently perturb the DNA double helix, distort the DNA conformation and interfere with accurate DNA replication, (b) Occasional errors are made during the cell processes for the repair of damaged DNA, such as DNA containing thymine dimers.

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