A model for targeted substitution mutagenesis during SOS replication of double-stranded DNA containing cis-syn...

A model for ultraviolet mutagenesis is described that is based on the formation of rare tautomeric bases in pyrimidine dimers. It is shown that during SOS synthesis the modified DNA-polymerase inserts canonical bases opposite the dimers; the inserted bases are capable of forming hydrogen bonds with bases in the template DNA. SOS-replication of double-stranded DNA having thymine dimers, with one or both bases in a rare tautomeric conformation, results in targeted transitions, transversions, or one-nucleotide gaps. Structural analysis indicates that one type of dimer containing a single tautomeric base (TT*(1), with the "*" indicating a rare tautomeric base and the subscript referring to the particular conformation) can cause A:T --> G:C transition or homologous A:T --> T:A transversion, while another dimer (TT*(2)) can cause a one-nucleotide gap. The dimers containing T*(4) result in A:T --> C:G transversion, while TT*(5) dimers can cause A:T --> C:G transversion or homologous A:T --> T:A transversion. If both bases in the dimer are in a rare tautomeric form, then tandem mutations or double-nucleotide gaps can be formed. The dimers containing the rare tautomeric forms T*'(1) , T*'(2), T*'(3), T*'(4), and T*'(5) may not result in mutations. The question of whether dimers containing T*'(4) and T*'(5) result in mutations requires further investigation.