The mechanism of switching among multiple BER pathways.

摘要: Abstract To preserve genomic β DNA from common endogenous and exogenous base sugar damage, cells are provided with multiple excision repair (BER) pathways: the polymerase (Pol) β-dependent single nucleotide BER long-patch (2–10 nt) that requires PCNA. It is a challenge to identify factors govern mechanism of switching among these pathways. One type damage induced in DNA. By using different model lesions we have shown damages (like hypoxanthine 1, N 6 -ethenoadenine) excised by monofunctional glycosylases repaired via both single-nucleotide BER, while bifunctional glycosylase 7,8-dihydro-8-oxoguanine) mainly BER. The presence genuine 5′ nucleotide, as case cleavage glycosylase-β lyase, would then minimize strand displacement events. Another key factor selection branch relative level cellular polymerases. While wild-type embryonic mouse fibroblast cell lines abasic sites predominantly replacement reactions (80% events), homozygous for deletion Pol gene exclusively Following treatment methylmethane sulfonate, mutant accumulate single-strand breaks their genome keeping fact alkylating agents goes Since strongly stimulated PCNA, content this cell-cycle regulated also extremely effective driving reaction either branch. These findings raise interesting possibility pathways might be acting function cycle stage.