Intrinsic 5'-deoxyribose-5-phosphate lyase activity in Saccharomyces cerevisiae Trf4 protein with a possible role in base excision DNA repair.

摘要: Abstract In Saccharomyces cerevisiae, the base excision DNA repair (BER) pathway has been thought to involve only a multinucleotide (long-patch) mechanism (LP-BER), in contrast most known cases that include major single-nucleotide (SN-BER). The key step mammalian SN-BER, removal of 5′-terminal abasic residue generated by AP endonuclease incision, is effected polymerase β (Polβ). Computational analysis indicates yeast Trf4 protein, with roles sister chromatin cohesion and RNA quality control, new member X family polymerases includes Polβ. Previous studies trf4Δ mutants revealed hypersensitivity methylmethane sulfonate (MMS) but not UV light, characteristic BER other organisms. We found that, like Polβ, able form Schiff intermediate 5′-deoxyribose-5-phosphate substrate excise through dRP lyase activity. Also forms stable cross-links vitro 5′-incised 2-deoxyribonolactone residues DNA. determined sensitivity MMS strains mutation rad27Δ background, an lyase-deficient background (ogg1 ntg1 ntg2), or pol4Δ background. Only RAD27 genetic interaction was detected: there higher for mutated both TRF4 than either single mutant, overexpression partially suppressed sensitivity. data strongly suggest role parallel Rad27-dependent LP-BER yeast. Finally, we demonstrate Trf5 significantly affects thus probably efficiency cells expressing wild-type C-terminus-deleted form.