DNA mismatch repair mediated by Mlh1-Pms1 endonuclease-catalyzed mispair excision.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41439704.
- Also identified by DOI 10.1073/pnas.2528670122 and PMC identifier 12772206.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Eukaryotic DNA mismatch repair (MMR) involves several excision pathways, including those mediated by exonuclease 1 (Exo1) and by the flap endonuclease Rad27 (human FEN1) coupled with DNA polymerase δ. Simultaneous inactivation of both excision mechanisms causes an MMR defect that is at most 5 to 13% of that caused by complete inactivation of MMR. Here, we reconstituted nicked-strand-specific MMR with the <i><i>Saccharomyces cerevisiae</i></i> proteins Msh2-Msh6 or Msh2-Msh3, DNA polymerase ε, RFC, PCNA, RPA, and Mlh1-Pms1 (human Mlh1-Pms2) under conditions lacking Exo1, Rad27, or strand-displacement synthesis by DNA polymerase δ. These reactions required the Mlh1-Pms1 endonuclease activity, its activation by RFC and PCNA, and its recruitment by Msh2-Msh6 or Msh2-Msh3. MMR was mediated by nicked-strand-specific excision by Mlh1-Pms1 through formation of single-strand DNA gaps having a broad range of sizes. This reaction is consistent with genetic data demonstrating redundancy between the Exo1, Rad27, and Mlh1-Pms1 excision pathways in MMR.
Medical subject headings
- DNA Mismatch Repair
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Adaptor Proteins, Signal Transducing