Synonyms
Historical Background
Exonuclease 1 (EXO1) was first identified in Schizosaccharomyces pombe (Szankasi and Smith 1995) and belongs to the Rad2/XPG family, which is conserved in its nuclease domain through species (Szankasi and Smith 1995; Wilson et al. 1998). The nuclease domain is located at the NH2-terminus and contains two subdomains the N-domain (N) and the internal (I) domain separated by a spacer region (Fig. 1). The EXO1 gene product exerts a 5′ → 3′ exonuclease and 5′ flap endonuclease activity (Lee and Wilson 1999; Keijzers et al. 2015). In addition, the EXO1 protein exhibits 5′ → 3′ intrinsic RNase H activity (Qiu et al. 1999). EXO1 has high affinity for processing double stranded DNA breaks (DSB), nicks, gaps, and pseudo-Y structures and can resolve double Holliday junctions. EXO1 is expressed at low level, independently of the cell cycle progression or proliferative status of the human cell (El-Shemerly et al. 2005). However, in...
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References
Andersen SD, Keijzers G, Rampakakis E, Engels K, Luhn P, El-Shemerly M, Nielsen FC, Du Y, May A, Bohr VA, Ferrari S, Zannis-Hadjopoulos M, Fu H, Rasmussen LJ. 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif. DNA Repair (Amst). 2012;11:267–77.
Bardwell PD, Woo CJ, Wei K, Li Z, Martin A, Sack SZ, Parris T, Edelmann W, Scharff MD. Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice. Nat Immunol. 2004;5:224–9.
Chen X, et al. 14-3-3 proteins restrain the Exo1 nuclease to prevent overresection. J Biol Chem. 2015;290:12300–12.
Cheruiyot A, Paudyal SC, Kim IK, Sparks M, Ellenberger T, Piwnica-Worms H, You Z. Poly(ADP-ribose)-binding promotes Exo1 damage recruitment and suppresses its nuclease activities. DNA Repair (Amst). 2015;35:106–15.
Eccleston J, Schrader CE, Yuan K, Stavnezer J, Selsing E. Class switch recombination efficiency and junction microhomology patterns in Msh2-, Mlh1-, and Exo1-deficient mice depend on the presence of mu switch region tandem repeats. J Immunol. 2009;183:1222–8.
Eccleston J, Yan C, Yuan K, Alt FW, Selsing E. Mismatch repair proteins MSH2, MLH1, and EXO1 are important for class-switch recombination events occurring in B cells that lack nonhomologous end joining. J Immunol. 2011;186:2336–43.
Eid W, Steger M, El-Shemerly M, Ferretti LP, Peña-Diaz J, König C, Valtorta E, Sartori AA, Ferrari S. DNA end resection by CtIP and exonuclease 1 prevents genomic instability. EMBO Rep. 2010;11:962–8.
El-Shemerly M, Janscak P, Hess D, Jiricny J, Ferrari S. Degradation of human exonuclease 1b upon DNA synthesis inhibition. Cancer Res. 2005;65:3604–9.
Gagné JP, Isabelle M, Lo KS, Bourassa S, Hendzel MJ, Dawson VL, Dawson TM, Poirier GG. Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes. Nucleic Acids Res. 2008;36:6959–76.
Iannascoli C, Palermo V, Murfuni I, Franchitto A, Pichierri P. The WRN exonuclease domain protects nascent strands from pathological MRE11/EXO1-dependent degradation. Nucleic Acids Res. 2015;43:9788–803.
Keijzers G, Maynard S, Shamanna RA, Rasmussen LJ, Croteau DL, Bohr VA. The role of RecQ helicases in non-homologous end-joining. Crit Rev Biochem Mol Biol. 2014;49:463–72.
Keijzers G, Bohr VA, Rasmussen LJ. Human exonuclease 1 (EXO1) activity characterization and its function on flap structures. Biosci Rep. 2015;35:e00206.
Keijzers G, Liu D, Rasmussen LJ. Exonuclease 1 and its versatile roles in DNA Repair. Crit Rev Biochem Mol Biol. 2016;51:440–51.
Kunkel TA, Erie DA. Eukaryotic mismatch repair in relation to DNA replication. Annu Rev Genet. 2015;49:291–313.
Lee BI, Wilson DM. The RAD2 domain of human exonuclease 1 exhibits 5″ to 3″ exonuclease and flap structure-specific endonuclease activities. J Biol Chem. 1999;274:37763–9.
Liberti SE, Andersen SD, Wang J, May A, Miron S, Perderiset M, Keijzers G, Nielsen FC, Charbonnier JB, Bohr VA, Rasmussen LJ. Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks. DNA Repair (Amst). 2011;10:73–86.
Liu Y, Kadyrov FA, Modrich P. PARP-1 enhances the mismatch-dependence of 5'-directed excision in human mismatch repair in vitro. DNA Repair (Amst). 2011;10:1145–53.
Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski S. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011;25:350–62.
Qiu J, Qian Y, Frank P, Wintersberger U, Shen B. Saccharomyces cerevisiae RNase H(35) functions in RNA primer removal during lagging-strand DNA synthesis, most efficiently in cooperation with Rad27 nuclease. Mol Cell Biol. 1999;19:8361–71.
Rein K, Yanez DA, Terré B, Palenzuela L, Aivio S, Wei K, Edelmann W, Stark JM, Stracker TH. EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele. Nucleic Acids Res. 2015;43:7371–87.
Schaetzlein S, Kodandaramireddy NR, Ju Z, Lechel A, Stepczynska A, Lilli DR, Clark AB, Rudolph C, Kuhnel F, Wei K, Schlegelberger B, Schirmacher P, Kunkel TA, Greenberg RA, Edelmann W, Rudolph KL. Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell. 2007;130:863–77.
Schaetzlein S, Chahwan R, Avdievich E, Roa S, Wei K, Eoff RL, Sellers RS, Clark AB, Kunkel TA, Scharff MD, Edelmann W. Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes. Proc Natl Acad Sci U S A. 2013;110:E2470–9.
Szankasi P, Smith GR. A role for exonuclease I from S. pombe in mutation avoidance and mismatch correction. Science. 1995;267:1166–9.
Tallis M, Morra R, Barkauskaite E, Ahel I. Poly(ADP-ribosyl)ation in regulation of chromatin structure and the DNA damage response. Chromosoma. 2014;123:79–90.
Wei K, Clark AB, Wong E, Kane MF, Mazur DJ, Parris T, Kolas NK, Russell R, Hou Jr H, Kneitz B, Yang G, Kunkel TA, Kolodner RD, Cohen PE, Edelmann W. Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Genes Dev. 2003;17:603–14.
Williams BR, Mirzoeva OK, Morgan WF, Lin J, Dunnick W, Petrini JH. A murine model of Nijmegen breakage syndrome. Curr Biol. 2002;12:648–53.
Wilson 3rd DM, Carney JP, Coleman MA, Adamson AW, Christensen M, Lamerdin JE. Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1. Nucleic Acids Res. 1998;26:3762–8.
Wu P, Takai H, de Lange T. Telomeric 3′ overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell. 2012;150:39–52.
Zhang F, Shi J, Chen SH, Bian C, Yu X. The PIN domain of EXO1 recognizes poly(ADP-ribose) in DNA damage response. Nucleic Acids Res. 2015;43:10782–94.
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Rasmussen, L.J., Keijzers, G. (2018). EXO1 (Exonuclease 1). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101686
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