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DNA polymerase chain reaction: A model of error frequencies and extension rates
Author(s) -
Griep Mark,
Whitney Scott,
Nelson Michael,
Viljoen Hendrik
Publication year - 2006
Publication title -
aiche journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.958
H-Index - 167
eISSN - 1547-5905
pISSN - 0001-1541
DOI - 10.1002/aic.10604
Subject(s) - polymerase chain reaction , sequence (biology) , extension (predicate logic) , polymerase , computational biology , dna , inverse polymerase chain reaction , word error rate , chain (unit) , fidelity , nucleotide , chemistry , dna polymerase , biological system , biology , topology (electrical circuits) , genetics , computer science , physics , mathematics , multiplex polymerase chain reaction , gene , combinatorics , telecommunications , astronomy , speech recognition , programming language
Abstract The polymerase chain reaction (PCR) is one of the most important reactions in molecular biology. The detailed mechanistic studies of the polymerase chain reaction have revealed a complex sequence of reversible reactions that involve intermediaries and activated complexes. The DNA polymerase does not merely facilitate the insertion of dNMP (deoxynucleotide monophosphates), but it also performs rapid screening of substrates to ensure a high degree of fidelity. The main result of this study is an expression for the average extension rate of the enzyme. The model is versatile and additional complexities, such as the type of nucleotide to be inserted, the GC content of the sequence in the vicinity of the insertion site, and the topology of the template, such as kinks and hairpins, are easy to incorporate. The insertion of incorrect nucleotides into the sequence is also addressed. Expressions to predict error frequencies are presented. It is shown that a relation exists between error frequency and extension rate: the error frequency is a minimum when the extension rate is optimal. © 2005 American Institute of Chemical Engineers AIChE J, 2006