Exonuclease 1 (EXO1)

HEX1; hExoI

SPN	U381
HGNC	3511
MGI	1349427
PubMed	12629043
RGD	1309465
UniProt	Q9UQ84
Wiki	Exonuclease_1

Exonuclease 1 is a protein with 5' to 3' exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms.5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch- containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment.

Reference

"Human exonuclease I interacts with the mismatch repair protein hMSH2."
Cancer Res. 58:4537-4542(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination."
Cancer Res. 58:5027-5031(1998) [PubMed] [Europe PMC] [Abstract]

"Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1."
Nucleic Acids Res. 26:3762-3768(1998) [PubMed] [Europe PMC] [Abstract]

"Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance."
J. Biol. Chem. 274:17893-17900(1999) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and biological annotation of human chromosome 1."
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The full-ORF clone resource of the German cDNA consortium."
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]

"The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities."
J. Biol. Chem. 274:37763-37769(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis."
Mutat. Res. 460:41-52(2000) [PubMed] [Europe PMC] [Abstract]

"The interaction of DNA mismatch repair proteins with human exonuclease I."
J. Biol. Chem. 276:33011-33018(2001) [PubMed] [Europe PMC] [Abstract]

"HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes."
Oncogene 20:3590-3595(2001) [PubMed] [Europe PMC] [Abstract]

"Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome."
Cancer Res. 62:6026-6030(2002) [PubMed] [Europe PMC] [Abstract]

"Human exonuclease I is required for 5' and 3' mismatch repair."
J. Biol. Chem. 277:13302-13311(2002) [PubMed] [Europe PMC] [Abstract]

"Molecular interactions of human Exo1 with DNA."
Nucleic Acids Res. 30:942-949(2002) [PubMed] [Europe PMC] [Abstract]

"Germline deletions of EXO1 do not cause colorectal tumors and lesions which are null for EXO1 do not have microsatellite instability."
Cancer Genet. Cytogenet. 147:121-127(2003) [PubMed] [Europe PMC] [Abstract]

"The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein."
J. Biol. Chem. 278:23487-23496(2003) [PubMed] [Europe PMC] [Abstract]

"Mechanism of 5'-directed excision in human mismatch repair."
Mol. Cell 12:1077-1086(2003) [PubMed] [Europe PMC] [Abstract]

"A defined human system that supports bidirectional mismatch-provoked excision."
Mol. Cell 15:31-41(2004) [PubMed] [Europe PMC] [Abstract]

"Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA."
Oncogene 23:1457-1468(2004) [PubMed] [Europe PMC] [Abstract]

"Reconstitution of 5'-directed human mismatch repair in a purified system."
Cell 122:693-705(2005) [PubMed] [Europe PMC] [Abstract]

"RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination."
J. Biol. Chem. 280:28085-28094(2005) [PubMed] [Europe PMC] [Abstract]

"Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1)."
Nucleic Acids Res. 35:2609-2619(2007) [PubMed] [Europe PMC] [Abstract]

"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]

"ATR-dependent pathways control hEXO1 stability in response to stalled forks."
Nucleic Acids Res. 36:511-519(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms."
Gastroenterology 120:1580-1587(2001) [PubMed] [Europe PMC] [Abstract]

"EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer."
Cancer Res. 63:154-158(2003) [PubMed] [Europe PMC] [Abstract]

"Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations."
Clin. Genet. 65:215-225(2004) [PubMed] [Europe PMC] [Abstract]

"Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population."
Carcinogenesis 26:411-416(2005) [PubMed] [Europe PMC] [Abstract]