MutL is the ATP-dependent coordinator and inferred strand-incision endonuclease of the MutH-independent mismatch repair pathway. It is recruited after MutS recognizes a replication mismatch, uses its N-terminal GHKL ATPase cycle to organize repair, and dimerizes through a C-terminal domain that is strongly inferred to nick duplex DNA. KT2440 lacks MutH, placing MutL-mediated incision in a methylation-independent repair architecture.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain as non-core. ATP binding supports the MutL conformational cycle, while ATP hydrolysis is the more informative catalytic function. Reason: Correct property of the N-terminal GHKL ATPase domain. |
| GO:0006259 DNA metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: This broad parent process adds no information beyond mismatch repair. Reason: GO:0006298 is the direct pathway term. |
| GO:0006298 mismatch repair | IEA GO_REF:0000120 | ACCEPT | Summary: Accept. Transient loss of MutL activity was used directly to expose the mismatch-correction hierarchy in KT2440. Reason: Core process with direct P. putida genetic support. Supporting Evidence: PMID:31599106 permanent deletion of mutS or transient loss of mutL activity |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accept as the catalytic function of the conserved GHKL ATPase domain. Reason: Pseudomonas MutL ATPase-site mutations cause defective mismatch repair, and Q88DD1 retains the conserved domain. Supporting Evidence: PMID:11952911 residue known to be essential for its ATPase activity. |
| GO:0030983 mismatched DNA binding | IEA GO_REF:0000002 | REMOVE | Summary: Remove. MutL can bind DNA in the repair complex, but mismatch-specific recognition is the role of MutS; direct mismatch specificity is not established for MutL. Reason: InterPro propagation conflates recruitment to mismatch-bound MutS with mismatch sensing. |
| GO:0032300 mismatch repair complex | IEA GO_REF:0000120 | ACCEPT | Summary: Accept. MutL is a defining component recruited by mismatch-bound MutS. Reason: Correct complex membership without assigning MutS's recognition function to MutL. |
| GO:0140664 ATP-dependent DNA damage sensor activity | IEA GO_REF:0000002 | REMOVE | Summary: Remove. MutL is an ATP-dependent coordinator and endonuclease recruited by MutS, not the protein that initially senses the mismatch. Reason: The sensor term belongs to MutS in this pathway. |
| GO:1990238 double-stranded DNA endonuclease activity | ISS PMID:23969026 Analysis of DNA structure and sequence requirements for Pseu... | NEW | Summary: Add by close-ortholog inference. Pseudomonas aeruginosa MutL directly nicks duplex plasmid DNA, and a reproducible global alignment finds 521 identical residues among 627 aligned residue pairs (83.1%) between its reviewed protein Q9HUL8 and KT2440 Q88DD1. Reason: The direct biochemical exemplar is a close Pseudomonas ortholog with the same MutH-independent architecture; a direct Q88DD1 assay is still needed. Supporting Evidence: PMID:23969026 PaMutL was able to nick covalently closed circular plasmids file:PSEPK/mutL/mutL-bioinformatics/RESULTS.md of which 521 are identical (83.0941%). |
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Download this section (compressed HTML)Q: Does Q88DD1 nick the nascent strand directly, and is its activity oriented or stimulated by the KT2440 beta clamp?
Experiment: Purify Q88DD1 and test metal-dependent nicking of covalently closed duplex DNA with MutS, mismatch-containing substrates, ATP/ADP, and the KT2440 beta clamp; compare catalytic-site and clamp-binding mutants.
Hypothesis: Q88DD1 is the strand-incision endonuclease of KT2440 MMR.
Type: reconstituted MutH-independent mismatch incision assay
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