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The ‘A rule’ of mutagen specificity: A consequence of DNA polymerase bypass of non‐instructional lesions?
Author(s) -
Strauss Bernard S.
Publication year - 1991
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.950130206
Subject(s) - proofreading , exonuclease , frameshift mutation , dna , dna polymerase , biology , dna damage , mutagen , dna synthesis , exonuclease iii , nucleotide excision repair , polymerase , mutation , base pair , mutagenesis , dna repair , biochemistry , gene , escherichia coli
The replicative bypass of lesions in DNA and the induction of mutations by agents which react with DNA to produce damaged bases can be understood on the basis of a simple kinetic model. Bypass can be analyzed by separately considering three processes: (a) addition of a base opposite a lesion, (b) a proofreading excision process, and (c) a rate limiting elongation step. Adenine nucleotides are preferentially added opposite many lesions making it possible to predict mutational specificity. Replicative bypass (translesion synthesis) is dependent on modulation of proofreading exonuclease activity but loss of exonuclease activity alone is not sufficient to ensure bypass. Frameshift mutation is the result of the failure of translesion synthesis accompanied by rearrangement of the template, particularly at repetitive sites.