Mismatch repair endonuclease PMS2; PMS1 protein homolog 2; DNA mismatch repair protein PMS2; postmeiotic segregation increased-2 (PMS2, PMSL2)

Function

• component of the post-replicative DNA mismatch repair system
• heterodimerizes with MLH1 to form mutL alpha
• DNA repair is initiated by mutS alpha (MSH2-MSH6) or mutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then mutL alpha is recruited to the heteroduplex
• assembly of the mutL-mutS-heteroduplex ternary complex in presence of RFC & PCNA is sufficient to activate endonuclease activity of PMS2
• it introduces single-strand breaks near the mismatch & thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch
• DNA methylation would prevent cleavage & therefore assure that only the newly mutated DNA strand is going to be corrected
• mulL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase 3, suggesting that it may play a role to recruit the DNA polymerase 3 to the site of the MMR
• also implicated in DNA damage signaling, a process which induces cell cycle arrest & can lead to apoptosis in case of major DNA damages
• heterodimer of PMS2 & MLH1 (mutL alpha)
• forms a ternary complex with mutS alpha (MSH2-MSH6) or mutS beta (MSH2-MSH3)
• part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 & the RAD50-MRE11-NBS1 protein complex; this association could be a dynamic process changing throughout the cell cycle & within subnuclear domains

Structure

• belongs to the DNA mismatch repair mutL/hexB family

Compartment

nucleus

Alternative splicing

named isoforms=4

Pathology

• defects in PMS2 are the cause of hereditary non-polyposis colorectal cancer type 4
• defects in PMS2 are a cause of mismatch repair cancer syndrome (Turcot syndrome)

Laboratory

• mismatch repair endonuclease PMS2 in cancer tissue

Comparative biology

• PMS2-/PMS2-knockout mice are viable, but male mice are sterile & appear to have a defect in meiosis.

More general terms

• mutL/PMS1 family protein
• nuclear protein
• phosphoprotein

Additional terms

• DNA mismatch repair protein Mlh1; mutL protein homolog 1 (MLH1, COCA2)
• DNA mismatch repair; post-replication repair; DNA loop repair

Component of

• MutL-alpha

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5395
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5395
• OMIM: https://mirror.omim.org/entry/276300
• OMIM: https://mirror.omim.org/entry/600259
• UniProt: http://www.uniprot.org/uniprot/P54278.html