Reactome | MSH2:MSH6 binds 1 base mismatch or 1-2 base insertion/deletion loop

MSH2:MSH6 binds 1 base mismatch or 1-2 base insertion/deletion loop

Stable Identifier

R-HSA-5358525

Type

Reaction

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

MutSalpha binds mismatch or 1-2 base insertion/deletion loop

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MSH2:MSH6 binds 1 base mismatch or 1-2 base insertion/deletion loop

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The MSH2:MSH6 (MutSalpha) heterodimer binds single base mismatches and insertion or deletion loops (IDLs) of 1-2 bases (Drummond et al. 1997, Genschel et al. 1998, Gradia et al. 2000, Zhang et al. 2005, Constantin et al. 2005, Tian et al. 2009, reviewed in Edelbrock et al. 2013). The MSH6 subunit contains a Phe-X-Glu motif that binds the mismatched base (Dufner et al 2000, Warren et al. 2007). During replication most nuclear MSH2:MSH6 is observed to colocalize with PCNA via an interaction between PCNA and MSH6 at replication forks during S phase (Kleczkowska et al. 2001), presumably coupling mismatch repair to DNA replication. The MSH6 subunit of MSH2:MSH6 also binds histone H3 methylated at lysine-36, which is enriched in chromatin during G1 and early S phase (Li et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
11274057	hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci Jiricny, J, Marra, G, Lettieri, T, Kleczkowska, HE	Genes Dev.	2001
19228687	Distinct nucleotide binding/hydrolysis properties and molar ratio of MutSalpha and MutSbeta determine their differential mismatch binding activities Li, GM, Tian, L, Gu, L	J. Biol. Chem.	2009
16143102	Reconstitution of 5'-directed human mismatch repair in a purified system Gao, Y, Zhang, Y, Li, GM, Yuan, F, Tian, K, Presnell, SR, Gu, L, Tomkinson, AE	Cell	2005
10938287	Mismatch recognition and DNA-dependent stimulation of the ATPase activity of hMutSalpha is abolished by a single mutation in the hMSH6 subunit Jiricny, J, Marra, G, Dufner, P, Räschle, M	J. Biol. Chem.	2000
23622243	The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutS? Huang, J, Mao, G, Li, F, Li, GM, Yang, W, Gu, L, Tong, D	Cell	2013
20160730	MutSbeta exceeds MutSalpha in dinucleotide loop repair Kariola, R, Korhonen, MK, Kantelinen, J, Nyström, M, Kansikas, M, Heinimann, K, Ollila, S	Br. J. Cancer	2010
23391514	Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities Kaliyaperumal, S, Williams, KJ, Edelbrock, MA	Mutat. Res.	2013
9677427	Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha Drummond, JT, Littman, SJ, Genschel, J, Modrich, P	J. Biol. Chem.	1998
10660545	The role of mismatched nucleotides in activating the hMSH2-hMSH6 molecular switch Gradia, S, Acharya, S, Fishel, R	J. Biol. Chem.	2000
16188885	Human mismatch repair: reconstitution of a nick-directed bidirectional reaction Dzantiev, L, Modrich, P, Kadyrov, FA, Constantin, N	J. Biol. Chem.	2005
17531815	Structure of the human MutSalpha DNA lesion recognition complex Modrich, PL, Pohlhaus, TJ, Warren, JJ, Changela, A, Beese, LS, Iyer, RR	Mol. Cell	2007
9294177	DHFR/MSH3 amplification in methotrexate-resistant cells alters the hMutSalpha/hMutSbeta ratio and reduces the efficiency of base-base mismatch repair Drummond, JT, Genschel, J, Wolf, E, Modrich, P	Proc. Natl. Acad. Sci. U.S.A.	1997