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

Stable Identifier
Homo sapiens
MutSalpha binds 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
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