Interruption of the MutS-B clamp interaction promotes mutations compatible with the PolIV activity

MARGARA LUCÍA M.; ARGARAÑA CARLOS E.; MONTI MARIELA R.

Mendoza

Congreso; XLVIII Reunión Anual de SAIB; 2012

The DNA mismatch repair (MMR) system corrects mismatched base pairs resulting mainly from DNA polymerase II replication errors. Interaction of the replication processivity factor B-clamp with the mismatch repair protein MutS is involved in early steps of MMR in eukaryotes and Bacillus sp. In a previous report, we demonstrated that the MutS-B clamp interaction does not play a role in the MMR of P. aeruginosa by characterizing a strain harboring a chromosomal allele (mutSB) which encodes a MutS mutant that does not interact with B-clamp. To establish the functional consequences of this interaction, we analyzed the nfxB mutation spectrum from the mutSB and parental strains. The mutSB strain, at difference of the parental strain, exhibited some mutations associated to the low fidelity DNA polymerase IV (PolIV) activity. Then, we determined the effect of enhance PolIV expression levels on the nfxB mutation spectrum. PolIV-associated mutations were increased in the mutSB strain whereas the nfxB mutation spectrum did not change in the parental strain. We propose that MutS could be limiting the action of PolIV by its interaction with B- clamp.