Increased repair replication in human lymphoid cells by inhibition of polyadenosine diphosphoribose synthesis with no increase in patch sizes.
Repair replication of alkylation damage in WIL-2 lymphoid cells is increased up to 7-fold by addition of 3-aminobenzamide, an inhibitor of polyadenosine diphosphoribose polymerase. This increase occurs without any change in the repair replication patch size and must therefore represent a large increase in the number of patches. The increase in the number of patches occurs without concomitant increase in the rate of excision of damaged sites. Therefore, it seems unlikely that 3-aminobenzamide plays any role in regulating ligation of repair patches, as commonly supposed. Instead, by inhibiting polyadenosine diphosphoribose polymerase or by other side effects, 3-aminobenzamide appears to elicit random nuclease attack of cellular DNA. The sites of attack are then repaired with patches of similar size, as are most other lesions. Nuclease attack may play a role in the increased cellular toxicity attendant on growth in 3-aminobenzamide.
D000178:Acrylamides; D001549:Benzamides / Q000494:pharmacology*; D002499:Centrifugation, Density Gradient; D004247:DNA / Q000032:analysis; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008970:Molecular Weight; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*
D000178:Acrylamides; D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D004247:DNA; D008741:Methyl Methanesulfonate