ArticleNucleic acids research2014
Biochemical characterization of a cancer-associated E109K missense variant of human exonuclease 1.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pooled it
- Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.Nucleic acids research · 2022Article
- FANCD2-Associated Nuclease 1 Partially Compensates for the Lack of Exonuclease 1 in Mismatch Repair.Molecular and cellular biology · 2021Article
- Human Exonuclease 1 (EXO1) Regulatory Functions in DNA Replication with Putative Roles in Cancer.International journal of molecular sciences · 2018Review
- Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae.PLoS genetics · 2017Article
- Influence of a single-nucleotide polymorphism of the DNA mismatch repair-related gene exonuclease-1 (rs9350) with prostate cancer risk among Chinese people.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Antibody diversification caused by disrupted mismatch repair and promiscuous DNA polymerases.DNA repair · 2016Review
- DNA mismatch repair and the DNA damage response.DNA repair · 2016Review
- Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis.OncoTargets and therapy · 2016Article
- FANCD2-associated nuclease 1, but not exonuclease 1 or flap endonuclease 1, is able to unhook DNA interstrand cross-links in vitro.The Journal of biological chemistry · 2015Article
- Human exonuclease 1 (EXO1) activity characterization and its function on flap structures.Bioscience reports · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the mismatch repair (MMR) genes MSH2, MSH6, MLH1 and PMS2 are associated with Lynch Syndrome (LS), a familial predisposition to early-onset cancer of the colon and other organs. Because not all LS families carry mutations in these four genes, the search for cancer-associated mutations was extended to genes encoding other members of the mismatch repairosome. This effort identified mutations in EXO1, which encodes the sole exonuclease implicated in MMR. One of these mutations, E109K, was reported to abrogate the catalytic activity of the enzyme, yet, in the crystal structure of the EXO1/DNA complex, this glutamate is far away from both DNA and the catalytic site of the enzyme. In an attempt to elucidate the reason underlying the putative loss of function of this variant, we expressed it in Escherichia coli, and tested its activity in a series of biochemical assays. We now report that, contrary to earlier reports, and unlike the catalytic site mutant D173A, the EXO1 E109K variant resembled the wild-type (wt) enzyme on all tested substrates. In the light of our findings, we attempt here to reinterpret the results of the phenotypic characterization of a knock-in mouse carrying the E109K mutation and cells derived from it.
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