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On the relations between error rates in DNA replication and elementary chemical rate constants
Authors:Jean Durup
Affiliation:Laboratoire des Collisions Atomiques et Moléculaires, Bât. 351, Université de Paris-Sud, 91405 Orsay, France
Abstract:A general treatment of the so-called peelback process is presented, where the final rates of errors in a simple model of DNA replication are derived from elementary chemical rate constants for incorporation or removal of correct or incorrect bases, in cases where these constants depend or not on the identity of the preceding base. It is shown that evidences regarding this dependence, for addition as well as for excision or pyrophosphorolysis, can be obtained from experimental determinations of the rate of appearance of various kinds of incorrect doublets in the final material and that these implications hold not only in the simple model case of a homopolynucleotide with a mixture of correct and incorrect substrates, but also in the real case of the four-bases DNA replication with the possibility of incorporation of incorrect bases instead of the correct ones in specific doublets. The connections between the various classes of parameters involved in a peelback process (instantaneous concentrations and lifetimes in final position, probabilities for ultimate fates, final contents of specific bases or doublets or triplets, etc.) are given in the Introduction.
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