LETHAL AND MUTAGENIC EFFECTS OF TRITIUM INCORPORATED INTO POSITION-8 OF PURINES IN PHAGE-LAMBDA DNA AND THE ROLE OF THE FPG PROTEIN

The lethal and mutagenic effects of the decay of H-3 incorporated in p hage lambda DNA as 8-H-3-adenosine and 8-H-3-guanosine were studied, u sing the DNA of 8-H-3-adenine as a labeled DNA precursor. A transmutat ion component of 3H decay is involved in formation of 8-oxoguanine (X- oxo-G) and 8-oxoadenine (X-oxo-A) residues in phage DNA. The efficienc y of phage inactivation (the number of lethal lesions per one tritium decay in the phage genome) for H-3 decay in position 8 of purines was the same as that measured in positions 5 and 6 of pyrimidines (alpha = 0.14 +/- 0.01) and virtually did not depend on the fpg-1::kan mutatio n in the host gene encoding the Fpg protein (formamidepyrimidine-DNA-g lycosylase). The efficiency of the mutagenic effect of H-3-purines E-m (frequency of c mutations per one H-3 decay in the phage genome) was (2.9 +/- 0.3) x 10(-5) in the fpg(+) host and (4.6 +/- 0.4) x 10(-5) i n the fpg(-) host. This means that the Fpg protein excised approximate ly 40% of premutational DNA lesions (probably, 8-oxo-G residues), Indu ction of the mutagenic SOS system by UV light-caused a 1.5-fold increa se in the frequency of c mutations induced by 8-H-3-purines in fpg(+) cells over that in fpg(-) cells. This suggests that apurinic AP sites produced after the excision of 8-oxo-G by the Fpg protein are substrat es for mutagenic SOS repair.