Meta-Biol

• Pathways

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).