Mutagenic effects of 2-deoxyribonolactone in Escherichia coli. An abasic lesion that disobeys the A-rule.

摘要: Abasic sites are often referred to as noninstructive lesions. The C1'-oxidized abasic site (2-deoxyribonolactone, L) is produced by several DNA damaging agents, including gamma-radiolysis and the neocarzinostatin chromophore (NCS). effects of a incorporated at defined in single-stranded plasmid were examined SOS polymerase-proficient -deficient Escherichia coli. For comparison, experiments utilizing plasmids containing an (AP) carried out side side. In contrast AP, dA dG most when L was replicated. ratio dG:dA incorporation depended upon local sequence varied from 0.9 2.2. High levels translesion consistent with previous observations that treatment resulted large amounts G.C --> A.T transitions [Povirk Goldberg (1986) Nucleic Acids Res. 14, 1417] support proposal source these mutations. Both lesions 100% lethal triple knockout cells lacking pol II, IV, V. Analysis synthesis repair-deficient revealed V played significant role replication AP. Significant -1 frameshifts formed 5'-d(CL) sequences presence exclusive product V-deficient cells. Frameshift products not nucleotide on 5'-side either dT or dG. Deleting II IV had only modest L-containing but significantly decreased amount frameshift AP lesion. Experiments using otherwise identical illustrate distinct properties two neither should be thought noninstructive.