EXO1 interacting with MSH2:MSH3 excises DNA strand containing an insertion/deletion loop (IDL)

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 (Zhang et al. 2005, Orans et al. 2011, and inferred from EXO1 activity with MSH2:MSH6) to create a single -stranded gap extending 90-170 nucleotides beyond the insertion/deletion loop (IDL) (Fang and Modrich 1993). 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
20970388 Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

Rasmussen, LJ, Miron, S, May, A, Bohr, VA, Liberti, SE, Wang, J, Charbonnier, JB, Andersen, SD, Keijzers, G, Nielsen, FC, Perderiset, M

DNA Repair (Amst.) 2011
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
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
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
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:MSH3:ATP:PCNA:DNA containing IDL of 2 or more bases and single strand incision [nucleoplasm]

Inferred From
Cite Us!