We measured the in vivo incororation of 2-aminopurine into DNA of T4 bacteriophage allelic for gene 43 (DNA polymerase), mutator (L56), 43+, and antimutator (L141). The magnitude of incorporation (mol/mol of Thy) was 1/1500 in L56, 1/1600 in 43+, and 1/8900 in L141. The incorporation ratio L56:43+:L141 in vivo was equal to that mediated by the purified DNA polymerases of these allelic phages in vitro. A model for 2-aminopurine-induced A*T ;-GC transitions is discussed. The model is used to predict the magnitudes of replication errors (C mispairing with a template 2-aminopurine) and incorporation errors (2-aminopurine mispairing with a template C) per round of replication and to investigate the asymmetry in 2-aminopurine-induced transitions favoring the A*T --GC pathway over G-C -A-T. We suggest that the fidelity of 156 and L141 DNA pol1erases exemplifies one-step and two-step editing, respectively. Error detection and correction is a process basic to the maintenance of informational integrity in biological systems. Genetic studies (1-7) demonstrated that certain temperature-sensitive bacteriophage T4 mutants (mutators and antimutators) having single base substitutions in gene 43, the gene coding for DNA polymerase (8), can exhibit increased and decreased mutation frequencies, respectively, as measured by the revision of marker loci. Measurements of the insertion and removal of 2-aminopurine (AP) deoxynucleotides by purified mutator and antimutator DNA polymerases during in vitro DNA synthesis revealed that the fidelity of DNA replication can be influenced by the polymerase-associated 3'-exonuclease (9, 10) or proofreading activity (11). Similar studies on the mispairing of normal nucleotides using defined polymer templates (12,13) further demonstrated that the insertion specificity may also influence the fidelity of the polymerization process.AP, a base analogue of adenine, induces transition mutations through the pathway: A-T >± AP-T ;=t AP-C ;=t G-C (14). In this paper, we address experimentally the initial and final steps in AP-induced A-T --G-C transitions. The first step is measured as AP incorporation into encapsulated DNA in T4 mutator (L56), wild-type (43+), and antimutator (L141) backgrounds. The final step is measured as the AP-induced reversion (A-T G-C transition) of the marker locus ri UV199 in gene 43 allelic bacteriophage (5,6). Both AP incorporation and APinduced transitions vary in a manner consistent with L56 mutator or L141 antimutator phenotypes. We will show that mutator and antimutator phage differ much more widely in AP-induced marker reversion than in AP incorporation. Because they respond differently to AP mutagenesis, the T4 phage must progress through the stages of AP-induced mutagenesis at significantly different rates. Therefore, it is possible to gain an intimate view of AP-induced mutagenesis and the role of A model of AP-induced transitions is proposed that facilitates analysis of the data by relating the population of each possible base pair in the transition pathway to ...

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315 e(t) = Z(t) -x(t).Now z and x are polynomials of order M -1 > 2N and 2N, respectively. The desired function x can be construed as a member of the larger calss of functions periodic in T and BL to f ( M -1)/2a2, hence e(t) must also be in that class. But e ( t ) must have RZ's at the M sampling points and is inadmissible unless identically zero. Hence 2 = 2. Second, we can remove the restriction that the number of samples per period be an integer exceeding 2N. This is done by recasting the earlier arguments in terms of a period T' = K T , where K is a positive integer. A number M , 2 2KN + 1 of samples per T' seconds suffices in such cases, and thus the minimal sampling rate approaches 2N samples per original period T rather than 2N + 1.