Abasic bypass

Figure 13.2 Comparison of bypass of abasic site analogs by different polymerases. Substrates containing the abasic analog THF can adopt at least two conformations during Dpo4-catalyzed bypass of the lesion, namely extrahelical (PDB ISON) and intrahelical (PDB 1S10) conformations. The intrahelical orientation represents what occurs following...

Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer. Genetics, 169, 575-582. 

Avkin, S., Adar, S., Blander, G., and Livneh, Z. (2002) Quantitative measurement of translesion replication in human cells evidence for bypass of abasic sites by a replicative DNA polymerase. Proc. Natl. Acad. Sci. USA, 99, 3764-3769. 

Otsuka, C., Loakes, D., and Negishi, K. (2002) The role of deoxycytidyl transferase activity of yeast Revl protein in the bypass of abasic sites. Nucleic Acids Res. Suppl., 2, 87-88. 

Fiala, K.A. and Suo, Z. (2007) Sloppy bypass of an abasic lesion catalyzed by a Y-family DNA polymerase. 

Gibbs, P.E., McDonald, J., Woodgate, R., and Lawrence, C.W. (2005) The relative roles in vivo of Saccharomyces cerevisiae Pol q, Pol Revl protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutyl dimer. Genetics, 169, 575-582. 

Bacteriophage SP6 RNA polymerase is blocked at single-strand breaks that form at an abasic site where the 2 -deoxyribose is present on either the 3 - or 5 -side of the nick, but bacteriophage T7 RNA polymerase bypasses abasic strand breaks... 

The apparent conflict between the in vivo and in vitro results may perhaps be explained by Revlp existing within a complex in the cell, in which dCMP insertion is inhibited at template sites other than those with abasic residues and, perhaps, some other lesions. Finally, the deoxycytidyl transferase activity, even if not essential for the bypass of abasic sites, nevertheless doubles the efficiency of rephcation past this lesion in yeast (Otsuka et al., 2002b see also Section III), perhaps explaining why the activity has been maintained throughout evolution. 

Lastly, Haracska and coworkers implicate Pol6 in the bypass of abasic sites because deletion of POL32, which encodes a nonessential subunit of this enzyme, essentially abolishes the induction of can mutations by MMS. This observation is unlikely to indicate the involvement of the catalytic function of Pol in the bypass of abasic sites, however, because such a function is by necessity present in the pol32A strain. More probably, the loss of the Pol32 subunit has an indirect influence on translesion... 

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