Involvement of the mismatch repair system in base analogue-induced mutagenesis

The influence of the mismatch repair system, and the role of mutS, mutR, and mutL genes, in mutagenesis induced by n2ome6Ade, n2oh6Ade and n2Pur have been investigated. From the frequency of reversion of Arg-Thr- and His- markers in AB2497, and its mut- derivatives, it was concluded that mismatches introduced by n2-ome6Ade and n2oh6Ade are better substrates for mismatch repair enzymes than that introduced by n2Pur. All these mut-gene products are more active in removing spontaneous or base analogue-induced mismatches which, when unexcised, lead to transversion of base repairs, than those which lead to transitions. Active engagements of mutL, mutR, or mutS gene products depend on the kind of mutation, the site of mutagenesis, and the inducing agent. Dam- cells are over-mutated by both n2ome6Ade and n2oh6Ade, but are hyper-sensitive to n2oh6Ade only. It is proposed that hyper-sensitivity of dam- cells is due not only to an increase in overlaping gap formation on both strands of DNA, but to a greater lability of the impaired cells. Results are presented which strongly suggest that n2ome6Ade in mut+ cells and n2oh6Ade in mut- only, can induce GC leads to TA transversions.