Molecular Basis of Mutation,DNA Replication,Tautomeric Shifts,MolecularStructures,Proton Migrations,Transitions

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Home >> Mutations >> Molecular Basis of Mutation

	Molecular Basis of Mutation - Even though DNA replication is based upon specific base pairing theoretically, in practice there are possibilities of occurrence of errors. Due to the non static nature of the bases present in DNA, the hydrogen atoms present in the amino group can move from one position in a purine or pyrimidine to another position. Such chemical fluctuations are called as tautomeric shifts. Tautomers are structural isomers that exist in equilibrium with one another. Tautomers of a single compound have the same chemical formulae but slightly different molecular structures. In pyrimidines (T and C), the hydrogen atoms shift from 3 atom (N) to 4 atom (0), whereas, purines (A,C) in the shift occurs between the number 1 and number 6.
Although tautomeric shifts are rare, the more stable keto form (thymine and guanine) and amino forms (adenine and cytosine) may undergo tautomeric shifts to a less stable enol and imino form for only very short period of time. But presence of such bases during DNA replication or repair" might result in a mutation. When the bases are present in their rare imino or enol states, they can form adenine cytosine and guanine-thymine base pairs. Mutations resulting from tautomeric shifts in the bases of DNA involve the replacement of a purine in one strand of DNA with the other purine and the replacement of a pyrimidine in the complementary stand with the other pyrimidine. Such base pair substitutions are called as transitions.
Proton migrations within base pairs can set a chain of modification that end up in mutation. Methylated guanine undergoes tautomeric shifts and pairs with thymine and leads to GC- T A transversions. Transversions occur by apposition of two errors-proton migration in one and 1800 rotation around glycoside bond (syn). Tautomeric synadenine (A ) may pair with Syn A which leads to AT - T A transversions. Similarly tautomeric neoguanine (G) may also pair with syn G which leads to GC-CG transversion. Even though all types of mutations are seen in various organisms, the probability of base deletions or addition is more than that of other mutations. Till now there is no clear explanation why this occurs. One point is clear, we have to learn a great deal about the cause and mechanism of mutation.

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