Reactome | MSH2:MSH6 exchanges ADP for ATP

MSH2:MSH6 exchanges ADP for ATP

Stable Identifier

R-HSA-5358912

Type

Reaction

Species

Homo sapiens

Compartment

nucleoplasm

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Summation

After binding a mismatch, the MSH2:MSH6 (MutSalpha) heterodimer exchanges ADP for ATP, which alters its conformation to a sliding clamp or molecular switch able to diffuse in one direction along duplex DNA (Gradia et al. 1997, Blackwell et al. 1998, Gradia et al. 1999, Gradia et al. 2000). Each heterodimer can bind 2 molecules of ATP or ADP or a combination of ADP and ATP. The affinities and hydrolysis rates of the binding sites differ (Tian et al. 2009, Heinen et al. 2011). However, the exact location of a given adenosine at a given binding location and the conferred function is unclear but believed to control downstream events. Hydrolysis of the ATP by MSH2:MSH6 is not required for mismatch binding but is required for subsequent mismatch repair (Gu et al. 1998, Tian et al. 2009, Geng et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
9428522	The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch Gradia, S, Acharya, S, Fishel, R	Cell	1997
19228687	Distinct nucleotide binding/hydrolysis properties and molar ratio of MutSalpha and MutSbeta determine their differential mismatch binding activities Tian, L, Gu, L, Li, GM	J. Biol. Chem.	2009
10660545	The role of mismatched nucleotides in activating the hMSH2-hMSH6 molecular switch Gradia, S, Acharya, S, Fishel, R	J. Biol. Chem.	2000
9469823	ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair Gu, L, Hong, Y, McCulloch, S, Watanabe, H, Li, GM	Nucleic Acids Res.	1998
9822680	Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism Blackwell, LJ, Martik, D, Bjornson, KP, Bjornson, ES, Modrich, P	J. Biol. Chem.	1998
21937421	Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-hMSH6 Heinen, CD, Cyr, JL, Cook, C, Punja, N, Sakato, M, Forties, RA, Lopez, JM, Hingorani, MM, Fishel, R	J. Biol. Chem.	2011
22277660	Biochemical analysis of the human mismatch repair proteins hMutS? MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D) Geng, H, Sakato, M, DeRocco, V, Yamane, K, Du, C, Erie, DA, Hingorani, M, Hsieh, P	J. Biol. Chem.	2012
10078208	hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA Gradia, S, Subramanian, D, Wilson, T, Acharya, S, Makhov, A, Griffith, J, Fishel, R	Mol. Cell	1999