MutS recognition of mismatches within primed DNA replication intermediates

BUSSETI, MILAGROS INÉS IBÁÑEZ; MARGARA, LUCÍA MALVINA; CASTELL, SOFÍA DAIANA; FERNÁNDEZ, MARISA MARIEL; MALCHIODI, EMILIO LUIS; MONTICH, GUILLERMO GABRIEL; MIGUEL, VIRGINIA; ARGARAÑA, CARLOS ENRIQUE; MONTI, MARIELA ROXANA

DNA REPAIR

ELSEVIER SCIENCE BV

Año: 2022 vol. 119

1568-7864

MutS initiates mismatch repair by recognizing mismatches in newly replicated DNA. Specific interactions between MutS and mismatches within double-stranded DNA promote ADP-ATP exchange and a conformational change into a sliding clamp. Here, we demonstrated that MutS from Pseudomonas aeruginosa associates with primed DNA replication intermediates. The predicted structure of this MutS-DNA complex revealed a new DNA binding site, in which Asn 279 and Arg 272 appeared to directly interact with the 3′-OH terminus of primed DNA. Mutation of these residues resulted in a noticeable defect in the interaction of MutS with primed DNA substrates. Remarkably, MutS interaction with a mismatch within primed DNA induced a compaction of the protein structure and impaired the formation of an ATP-bound sliding clamp. Our findings reveal a novel DNA binding mode, conformational change and intramolecular signaling for MutS recognition of mismatches within primed DNA structures.