Reactome | EXO1 interacting with MSH2:MSH6 excises single strand DNA containing a mismatch

EXO1 interacting with MSH2:MSH6 excises single strand DNA containing a mismatch

Stable Identifier

R-HSA-5358599

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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EXO1 interacting with MSH2:MSH6 excises single strand DNA containing a mismatch

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EXO1 exonucleolytically degrades the strand being repaired in a 5' to 3' direction (Genschel et al. 2002, Genschel and Modrich 2003, Dzantiev et al. 2004, Zhang et al. 2005, Constantin et al. 2005, Genschel and Modrich 2006, Orans et al. 2011) to create a single -stranded gap extending 90-170 nucleotides beyond the mismatch (Fang and Modrich 1993). Interaction of MSH2:MSH6 (MutSalpha) with EXO1 reduces the exonuclease activity of EXO1 on correctly paired DNA duplexes (Orans et al. 2011). MLH1:PMS2 limits the length of excisions by EXO1 (Zhang et al. 2005). EXO1 also forms a complex with PCNA during S phase (Liberti et al. 2011). RPA binds the resulting single-stranded DNA (Lin et al. 1998, Ramilo et al. 2002, Zhang et al. 2005, reviewed in Iftode et al. 1999).

Literature References

PubMed ID	Title	Journal	Year
8505312	Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction Fang, WH, Modrich, P	J. Biol. Chem.	1993
10473346	Replication protein A (RPA): the eukaryotic SSB. Iftode, C, Daniely, Y, Borowiec, JA	Crit Rev Biochem Mol Biol	1999
16143102	Reconstitution of 5'-directed human mismatch repair in a purified system Zhang, Y, Yuan, F, Presnell, SR, Tian, K, Gao, Y, Tomkinson, AE, Gu, L, Li, GM	Cell	2005
11809771	Human exonuclease I is required for 5' and 3' mismatch repair Genschel, J, Bazemore, LR, Modrich, P	J. Biol. Chem.	2002
9430682	The evolutionarily conserved zinc finger motif in the largest subunit of human replication protein A is required for DNA replication and mismatch repair but not for nucleotide excision repair Lin, YL, Shivji, MK, Chen, C, Kolodner, R, Wood, RD, Dutta, A	J. Biol. Chem.	1998
14636568	Mechanism of 5'-directed excision in human mismatch repair Genschel, J, Modrich, P	Mol. Cell	2003
16188885	Human mismatch repair: reconstitution of a nick-directed bidirectional reaction Constantin, N, Dzantiev, L, Kadyrov, FA, Modrich, P	J. Biol. Chem.	2005
15225546	A defined human system that supports bidirectional mismatch-provoked excision Dzantiev, L, Constantin, N, Genschel, J, Iyer, RR, Burgers, PM, Modrich, P	Mol. Cell	2004
11884592	Partial reconstitution of human DNA mismatch repair in vitro: characterization of the role of human replication protein A Ramilo, C, Gu, L, Guo, S, Zhang, X, Patrick, SM, Turchi, JJ, Li, GM	Mol. Cell. Biol.	2002
16793375	Analysis of the excision step in human DNA mismatch repair Genschel, J, Modrich, P	Meth. Enzymol.	2006
21496642	Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family Orans, J, McSweeney, EA, Iyer, RR, Hast, MA, Hellinga, HW, Modrich, P, Beese, LS	Cell	2011