DNA mismatch repair (Homo sapiens)

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1, 2MutLalpha5' MMRExcisionTCPOLEATPEXO1POLD1LIG1LigationPOLD2POLD3POLD4Re-synthesisTCRFC1MSH6MSH2PCNARFC2RFC3RFC4RFC5MutSPMS2MLH15'5'3'3'5'3'5'3'RPA1RPA3RPA2MSH3MSH2EXO1RPA1RPA3RPA2MSH6MSH2MSH3MSH25'3'5'3'MSH6MSH2MSH3MSH2PMS2MLH1EXO1PCNARPA1RPA3RPA2POLE2POLE3POLE4RPA1RPA3RPA25'3'5'3'5'3'5'3'TC5'5'3'3'3' MMRMSH6MSH2MutSMSH3MSH2Mismatch recognitionPCNAATPMutLalphaPMS2MLH1POLEPOLD1POLD2POLD3POLD4POLE2POLE3POLE4TC3'5'5'3'PCNAMSH6MSH2MSH3MSH2PMS2MLH13'5'5'3'RPA1RPA3RPA2RPA1RPA3RPA23'5'5'3'RPA1RPA3RPA2PCNALIG1POLEPOLE2POLE3POLE4POLD1POLD2POLD3POLD45'3'5'3'LIG1LIG1POLEPOLE2POLE3POLE4POLD1POLD2POLD3POLD4


Description

DNA mismatch repair (MMR) is responsible for correcting mismatches and small insertions and deletions caused during replication and recombination. In eukaryotes the process of MMR is initiated by MutSalpha and MutLalpha, homologs of the E.coli proteins MutS and MutL. MutS homologs first recognize the error in DNA, and then physically interact with MutL, which activates other proteins that remove the erroneous DNA strand and synthesize a new one.

In vitro MMR requires a nick requires a preexisting nick (single-strand gap) in the DNA substrate. Similarly, it is thought that for in vivo MMR in eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) which provides a signal that directs mismatch proofreading systems to the appropriate strandThis pathway describes the slightly different mechanisms for MMR based on the location of the nick in relation to the mismatch (5' and 3').

Mutations in the genes coding human MutS and MutL homologs have been linked with the Lynch syndrome, which is characterized by an increased risk of developing cancer.

This pathway is based on figure 1 from Hsieh et al, with additional information from REPAIRtoire, Wikipedia and KEGG. The description was adapted from REPAIRtoire, layout is based on KEGG.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

  1. Hsieh P, Zhang Y; ''The Devil is in the details for DNA mismatch repair.''; Proc Natl Acad Sci U S A, 2017 PubMed Europe PMC Scholia
  2. Iyer RR, Pluciennik A, Burdett V, Modrich PL; ''DNA mismatch repair: functions and mechanisms.''; Chem Rev, 2006 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
117702view12:23, 22 May 2021EweitzModified title
113644view18:17, 9 November 2020EgonwReplaced old HMDB identifiers.
110621view18:03, 21 May 2020Khanspersclearer diagram
110620view17:13, 21 May 2020KhanspersModified description
110610view05:39, 21 May 2020KhanspersAdded more 3' MMR
110609view00:11, 21 May 2020Khanspersadded 3' MMR
110608view00:04, 21 May 2020Khansperswork in progress
110607view23:35, 20 May 2020Khansperswork in progress
110606view23:15, 20 May 2020Khansperswork in progress
108607view05:19, 10 January 2020Khanspersfixed ordering
108606view05:18, 10 January 2020KhanspersModified description
108605view05:12, 10 January 2020KhanspersOntology Term : 'mismatch repair pathway' added !
108604view05:12, 10 January 2020KhanspersOntology Term : 'DNA repair pathway' added !
108603view05:11, 10 January 2020Khanspersclarified complexes
108602view03:32, 10 January 2020Khanspersoverhaul
108598view23:56, 9 January 2020Khanspersupdated layout, style etc
106649view21:11, 12 September 2019Khanspersfixed interaction
106648view21:09, 12 September 2019KhanspersModified description
105502view05:55, 8 August 2019KhanspersModified description
102350view17:05, 20 December 2018KhanspersModified title
102349view17:05, 20 December 2018KhanspersModified title
102348view17:04, 20 December 2018Khanspersconverted interactions to graphical lines
69021view17:49, 8 July 2013MaintBotUpdated to 2013 gpml schema
59206view19:50, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
41198view23:43, 1 March 2011MaintBotRemoved redundant pathway information and comments
36296view23:21, 17 March 2010KhanspersModified categories
35172view14:57, 11 February 2010Thomasadded literature ref
35171view14:54, 11 February 2010Thomascolor fix
35170view14:53, 11 February 2010ThomasModified description
35169view14:52, 11 February 2010Thomassolid shapes
29611view12:09, 23 May 2009MartijnVanIerselUpdated ensembl references
21796view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:Mismatch repair]] moved to [[Pathway:WP531]]: Moved to stable identifier
20396view21:16, 3 November 2008AlexanderPicofixed species info
10357view03:01, 23 January 2008AlexanderPicoModified categories
9590view10:51, 9 January 2008Thomasadded mismatch repair pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ATPMetaboliteHMDB0000538 (HMDB)
EXO1GeneProductENSG00000174371 (Ensembl)
LIG1GeneProductENSG00000105486 (Ensembl)
MLH1GeneProductENSG00000076242 (Ensembl)
MSH2GeneProductENSG00000095002 (Ensembl)
MSH3GeneProductENSG00000116062 (Ensembl)
MSH6GeneProductENSG00000116062 (Ensembl)
PCNAGeneProductENSG00000132646 (Ensembl)
PMS2GeneProductENSG00000122512 (Ensembl)
POLD1GeneProductENSG00000062822 (Ensembl)
POLD2GeneProductENSG00000106628 (Ensembl)
POLD3GeneProductENSG00000077514 (Ensembl)
POLD4GeneProductENSG00000175482 (Ensembl)
POLE2GeneProductENSG00000100479 (Ensembl)
POLE3GeneProductENSG00000148229 (Ensembl)
POLE4GeneProductENSG00000115350 (Ensembl)
POLEGeneProductENSG00000177084 (Ensembl)
RFC1GeneProductENSG00000035928 (Ensembl)
RFC2GeneProductENSG00000049541 (Ensembl)
RFC3GeneProductENSG00000133119 (Ensembl)
RFC4GeneProductENSG00000163918 (Ensembl)
RFC5GeneProductENSG00000111445 (Ensembl)
RPA1GeneProductENSG00000132383 (Ensembl)
RPA2GeneProductENSG00000117748 (Ensembl)
RPA3GeneProductENSG00000106399 (Ensembl)

Annotated Interactions

No annotated interactions

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