A model for targeted substitution mutagenesis during SOS replication of double-stranded DNA containing cis-syn cyclobutane thymine dimers.
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.
Grebneva
Helen A
HA
Donetsk Physical and Technical Institute, National Academy of Science of Ukraine, Donetsk, Ukraine. grebneva@gmail.com
D004247:DNA / Q000528:radiation effects; D008958:Models, Molecular; D016296:Mutagenesis; D011740:Pyrimidine Dimers / Q000235:genetics*; D013014:SOS Response, Genetics; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D004247:DNA