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

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

Stable Identifier

R-HSA-5358606

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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

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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
11920679	DNA mismatch repair and mutation avoidance pathways Marti, TM, Fleck, O, Kunz, C	J. Cell. Physiol.	2002
8805365	hMutSbeta, a heterodimer of hMSH2 and hMSH3, binds to insertion/deletion loops in DNA Jiricny, J, Iaccarino, I, Palombo, F, Shimada, T, Nakajima, E, Ikejima, M	Curr. Biol.	1996
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
9671718	Mismatch repair deficiency associated with overexpression of the MSH3 gene Jiricny, J, Roscilli, G, Iaccarino, I, Marra, G, Lettieri, T, Delmastro, P	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