Tomas Lindahl (2017) - DNA Instability, Endogenous Mutagenesis, and DNA Repair

Tomas Lindahl (2017)

DNA Instability, Endogenous Mutagenesis, and DNA Repair

Tomas Lindahl (2017)

DNA Instability, Endogenous Mutagenesis, and DNA Repair

Abstract

Although DNA is the carrier of genetic information, it is chemically a relatively unstable macromolecule. The major decay occurring under physiological conditions is due to hydrolytic loss of guanine and adenine to generate apurinic sites. This involves loss of genetic information. Other relevant changes include deamination of cytosines to miscoding uracil residues. Several DNA repair mechanisms have evolved to counteract such endogenous damage, including the base excision repair pathway. This is initiated by one of several specific DNA glycosylases that catalyses the removal of an altered base residue. Other forms of relevant DNA damage due to this enemy within include lesions caused by reaction with active oxygen, or the co enzyme S adenosylmethionine to generate lethal or mutagenic alterations. Several of these lesions are repaired by special enzymatic mechanisms not employed by other forms of DNA metabolism.

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