Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)

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R-HSA-5358606
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Pathway
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Homo sapiens
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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.

Literature References
PubMed ID Title Journal Year
8805365 hMutSbeta, a heterodimer of hMSH2 and hMSH3, binds to insertion/deletion loops in DNA

Palombo, F, Iaccarino, I, Nakajima, E, Ikejima, M, Shimada, T, Jiricny, J

Curr. Biol. 1996
11920679 DNA mismatch repair and mutation avoidance pathways

Marti, TM, Kunz, C, Fleck, O

J. Cell. Physiol. 2002
9677427 Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha

Genschel, J, Littman, SJ, Drummond, JT, Modrich, P

J. Biol. Chem. 1998
9671718 Mismatch repair deficiency associated with overexpression of the MSH3 gene

Marra, G, Iaccarino, I, Lettieri, T, Roscilli, G, Delmastro, P, Jiricny, J

Proc. Natl. Acad. Sci. U.S.A. 1998
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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