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

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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.

Daniely, Y, Borowiec, JA, Iftode, C

Crit Rev Biochem Mol Biol 1999
16143102 Reconstitution of 5'-directed human mismatch repair in a purified system

Gao, Y, Zhang, Y, Li, GM, Yuan, F, Tian, K, Presnell, SR, Gu, L, Tomkinson, AE

Cell 2005
11809771 Human exonuclease I is required for 5' and 3' mismatch repair

Modrich, P, Genschel, J, Bazemore, LR

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

Shivji, MK, Lin, YL, Wood, RD, Dutta, A, Chen, C, Kolodner, R

J. Biol. Chem. 1998
14636568 Mechanism of 5'-directed excision in human mismatch repair

Modrich, P, Genschel, J

Mol. Cell 2003
16188885 Human mismatch repair: reconstitution of a nick-directed bidirectional reaction

Dzantiev, L, Modrich, P, Kadyrov, FA, Constantin, N

J. Biol. Chem. 2005
15225546 A defined human system that supports bidirectional mismatch-provoked excision

Dzantiev, L, Modrich, P, Burgers, PM, Iyer, RR, Genschel, J, Constantin, N

Mol. Cell 2004
11884592 Partial reconstitution of human DNA mismatch repair in vitro: characterization of the role of human replication protein A

Patrick, SM, Guo, S, Zhang, X, Li, GM, Ramilo, C, Turchi, JJ, Gu, L

Mol. Cell. Biol. 2002
16793375 Analysis of the excision step in human DNA mismatch repair

Modrich, P, Genschel, J

Meth. Enzymol. 2006
21496642 Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family

Hellinga, HW, McSweeney, EA, Modrich, P, Beese, LS, Iyer, RR, Orans, J, Hast, MA

Cell 2011
Catalyst Activity

5'-3' exonuclease activity of EXO1:MLH1:PMS2:MSH2:MSH6:ATP:PCNA:DNA containing 1-2 base mismatch and single strand incision [nucleoplasm]

Orthologous Events
Cite Us!