MSH2:MSH3 (MutSbeta) binds unpaired loops of 2 or more nucleotides (Palombo et al. 1996, Genschel et al. 1998). Human cells contain about 6-fold more MSH2:MSH6 than MSH2:MSH3 (MutSbeta) and an imbalance in the ratio can cause a mutator phenotype (Drummond et al. 1997, Marra et al. 1998). Binding of the mismatch activates MSH2:MSH3 to exchange ADP for ATP, adopt the conformation to allow movement along the DNA, and interact with downstream effectors PCNA, MLH1:PMS2 and EXO1. The interaction with PCNA initiates excision of the recently replicated strand. MLH1:PMS2 makes a nick that is enlarged to a gap of hundreds of nucleotides by EXO1. DNA is polymerized across the gap by DNA polymerase delta and the remaining nick is sealed by DNA ligase I.
Marti, TM, Fleck, O, Kunz, C
Jiricny, J, Iaccarino, I, Palombo, F, Shimada, T, Nakajima, E, Ikejima, M
Drummond, JT, Littman, SJ, Genschel, J, Modrich, P
Jiricny, J, Roscilli, G, Iaccarino, I, Marra, G, Lettieri, T, Delmastro, P
Drummond, JT, Genschel, J, Wolf, E, Modrich, P
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