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Exo1  -  exonuclease 1

Mus musculus

Synonyms: 5730442G03Rik, Exonuclease 1, Exonuclease I, Msa, mExo1
 
 
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Disease relevance of Exo1

 

High impact information on Exo1

  • Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis [1].
  • The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus [1].
  • Mononucleotide breakdown products appeared rapidly in circulation with no lag phase, suggesting that exonuclease activity was not dependent upon prior phagocytosis [5].
  • Since no exonuclease activity could be demonstrated in plasma in vitro, it was postulated that breakdown of ssDNA by exonucleases occurs on the surface of hepatocytes of Kupffer cells [5].
  • The B-1a subset is characterized by a low N-region diversity, by a high frequency of sequence homologies in the VH-D and D-JH junctions, and by a limited exonuclease nibbling of the terminals of the joining gene segments [6].
 

Chemical compound and disease context of Exo1

 

Biological context of Exo1

  • Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis [1].
  • These results suggested that the testicular meiotic Msa in MRL/MpJ mice was a unique phenotype caused by incomplete alternative splicing of the Exo1 gene [8].
  • Mutation of the Exo1 gene was previously reported to be responsible for metaphase-specific apoptosis (MSA) of spermatocytes in the MRL/MpJ mouse [2].
  • Comparative evaluation of the expression patterns of the human and mouse genes, combined with previous biochemical and yeast genetic studies, indicate that the Exo1-like proteins are important contributors to chromosome processing during mammalian DNA repair and recombination [9].
  • Probing the roles of active site residues in the 3'-5' exonuclease of the werner syndrome protein [10].
 

Anatomical context of Exo1

  • Furthermore, we demonstrated that mouse embryonic fibroblasts, deficient in the exonuclease activity of Pol delta are partially deficient in the repair of these 'complex' lesions, demonstrating the importance of Pol delta during the repair of DNA lesions in close proximity to a DNA SSB, typical of those induced by ionizing radiation [11].
  • High expression of a 3'----5' exonuclease activity is specific to B lymphocytes [12].
  • A new marker for human secretory epithelial cell types (Exo-1) has been defined by a mouse monoclonal antibody (Pa-G14) [13].
  • An exonuclease III assay (Wu, C. (1985) Nature 317, 84-87) was used to identify in nuclear extracts of NIH 3T3 cells a factor which binds to the CCAAT segment of the alpha 2(I) collagen promoter between -80 and -84 [14].
  • Stimulation of murine B lymphocytes induces a DNA exonuclease whose activity on switch-mu DNA is specifically inhibited by other germ-line switch region RNAs [15].
 

Associations of Exo1 with chemical compounds

  • We used an in situ exonuclease III protection technique (C. Wu, Nature [London] 309:229, 1984) to analyze protein-DNA interactions at a dioxin-responsive enhancer [16].
  • In cultured Exo-1 positive tumor cells the antigen was not demonstrable on the cell surface but in the cytoplasm after acetone/methanol fixation only [13].
  • Both exonuclease activities co-migrated with the polymerase activity during the final purification step of polyacrylamide gradient gel electrophoresis, which yielded the essentially homogenous alpha-polymerase, and also during sedimentation of the purified enzyme through a high salt glycerol gradient [17].
  • Several lines of evidence suggest that the PAAr mutations primarily affect the deoxynucleoside triphosphate-binding site, whereas the codon 171 mutation, lying within a conserved motif associated with 3'-5' exonuclease function, is postulated to affect the proofreading exonuclease of the DNA polymerase [18].
  • To confirm the nucleosome positions determined with the hydroxyl radical assay, nucleosome boundaries were mapped using exonuclease III [19].
 

Other interactions of Exo1

 

Analytical, diagnostic and therapeutic context of Exo1

  • Using alkaline denaturation-renaturation, exonuclease III digestion and density gradient centrifugations, we have isolated covalently closed circular DNA (cccDNA) molecules from 1-, 8-, 16-, and 24-month C57BL/6 mouse heart tissues [24].
  • Oocyte and embryo 5' --> 3' exonuclease (a key function of the SSA pathway) and DNA nonhomologous end joining (NHEJ) activities were also investigated using an asymmetric PCR assay [25].
  • The efficiency of the exonuclease method was compared to ultracentrifugation techniques and was found to give yields greater than those obtained by two or more equilibrium density gradients [26].
  • Exonuclease activity measurement and epitope mapping revealed that the epitope for 3G8 is located in conserved regions among alpha-like (family B) DNA polymerases (Region II), and the epitope for betaG1 is located in the 3'-5' exonuclease domain [27].
  • Properties of exonuclease-resistant, psoralen-conjugated oligodeoxyribonucleotides in vitro and in cell culture [28].

References

  1. Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Wei, K., Clark, A.B., Wong, E., Kane, M.F., Mazur, D.J., Parris, T., Kolas, N.K., Russell, R., Hou, H., Kneitz, B., Yang, G., Kunkel, T.A., Kolodner, R.D., Cohen, P.E., Edelmann, W. Genes Dev. (2003) [Pubmed]
  2. Quantitative trait loci analysis of heat stress resistance of spermatocytes in the MRL/MpJ mouse. Namiki, Y., Kon, Y., Kazusa, K., Asano, A., Sasaki, N., Agui, T. Mamm. Genome (2005) [Pubmed]
  3. Steroid-dependent interaction of transcription factors with the inducible promoter of mouse mammary tumor virus in vivo. Cordingley, M.G., Riegel, A.T., Hager, G.L. Cell (1987) [Pubmed]
  4. Inhibition of bacterial DNA replication by zinc mobilization during nitrosative stress. Schapiro, J.M., Libby, S.J., Fang, F.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Kinetics and mechanisms for removal of circulating single-stranded DNA in mice. Emlen, W., Mannik, M. J. Exp. Med. (1978) [Pubmed]
  6. B-1a, B-1b and B-2 B cells display unique VHDJH repertoires formed at different stages of ontogeny and under different selection pressures. Tornberg, U.C., Holmberg, D. EMBO J. (1995) [Pubmed]
  7. An exonuclease possibly involved in the initiation of repair of bleomycin-damaged DNA in mouse ascites sarcoma cells. Seki, S., Oda, T. Carcinogenesis (1988) [Pubmed]
  8. Genetic mutation associated with meiotic metaphase-specific apoptosis in MRL/MpJ mice. Namiki, Y., Endoh, D., Kon, Y. Mol. Reprod. Dev. (2003) [Pubmed]
  9. Expression specificity of the mouse exonuclease 1 (mExo1) gene. Lee, B.I., Shannon, M., Stubbs, L., Wilson, D.M. Nucleic Acids Res. (1999) [Pubmed]
  10. Probing the roles of active site residues in the 3'-5' exonuclease of the werner syndrome protein. Choi, J.M., Kang, S.Y., Bae, W.J., Jin, K.S., Ree, M., Cho, Y. J. Biol. Chem. (2007) [Pubmed]
  11. DNA polymerase delta-dependent repair of DNA single strand breaks containing 3'-end proximal lesions. Parsons, J.L., Preston, B.D., O'Connor, T.R., Dianov, G.L. Nucleic Acids Res. (2007) [Pubmed]
  12. High expression of a 3'----5' exonuclease activity is specific to B lymphocytes. Kenter, A.L., Tredup, J. Mol. Cell. Biol. (1991) [Pubmed]
  13. Secretory epithelial cell marker on gastrointestinal tumors and in human secretions defined by a monoclonal antibody. Dippold, W.G., Klingel, R., Bernhard, H., Dienes, H.P., Knuth, A., Meyer zum Büschenfelde, K.H. Cancer Res. (1987) [Pubmed]
  14. Differential binding of a CCAAT DNA binding factor to the promoters of the mouse alpha 2(I) and alpha 1(III) collagen genes. Hatamochi, A., Paterson, B., de Crombrugghe, B. J. Biol. Chem. (1986) [Pubmed]
  15. Stimulation of murine B lymphocytes induces a DNA exonuclease whose activity on switch-mu DNA is specifically inhibited by other germ-line switch region RNAs. Müller, J.R., Marcu, K.B. J. Immunol. (1998) [Pubmed]
  16. In situ protein-DNA interactions at a dioxin-responsive enhancer associated with the cytochrome P1-450 gene. Durrin, L.K., Whitlock, J.P. Mol. Cell. Biol. (1987) [Pubmed]
  17. Mouse DNA polymerase alpha. Subunit structure and identification of a species with associated exonuclease. Chen, Y.C., Bohn, E.W., Planck, S.R., Wilson, S.H. J. Biol. Chem. (1979) [Pubmed]
  18. Genetic characterization of the vaccinia virus DNA polymerase: cytosine arabinoside resistance requires a variable lesion conferring phosphonoacetate resistance in conjunction with an invariant mutation localized to the 3'-5' exonuclease domain. Taddie, J.A., Traktman, P. J. Virol. (1993) [Pubmed]
  19. Nucleosomes reconstituted in vitro on mouse mammary tumor virus B region DNA occupy multiple translational and rotational frames. Roberts, M.S., Fragoso, G., Hager, G.L. Biochemistry (1995) [Pubmed]
  20. Binding in vitro of multiple cellular proteins to immunoglobulin heavy-chain enhancer DNA. Peterson, C.L., Orth, K., Calame, K.L. Mol. Cell. Biol. (1986) [Pubmed]
  21. Effect of wild-type, S15D and R175H p53 proteins on DNA end joining in vitro: potential mechanism of DNA double-strand break repair modulation. Okorokov, A.L., Warnock, L., Milner, J. Carcinogenesis (2002) [Pubmed]
  22. DNA variants with telomere probe enable genetic mapping of ends of mouse chromosomes. Elliott, R.W., Yen, C.H. Mamm. Genome (1991) [Pubmed]
  23. High incidence of epithelial cancers in mice deficient for DNA polymerase delta proofreading. Goldsby, R.E., Hays, L.E., Chen, X., Olmsted, E.A., Slayton, W.B., Spangrude, G.J., Preston, B.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  24. Characterization of repetitive sequence families in mouse heart small polydisperse circular DNAs: age-related studies. Flores, S.C., Sunnerhagen, P., Moore, T.K., Gaubatz, J.W. Nucleic Acids Res. (1988) [Pubmed]
  25. Growing dictyate oocytes, but not early preimplantation embryos, of the mouse display high levels of DNA homologous recombination by single-strand annealing and lack DNA nonhomologous end joining. Fiorenza, M.T., Bevilacqua, A., Bevilacqua, S., Mangia, F. Dev. Biol. (2001) [Pubmed]
  26. Purification of eucaryotic extrachromosomal circular DNAs using exonuclease III. Gaubatz, J.W., Flores, S.C. Anal. Biochem. (1990) [Pubmed]
  27. Characterization and application to hot start PCR of neutralizing monoclonal antibodies against KOD DNA polymerase. Mizuguchi, H., Nakatsuji, M., Fujiwara, S., Takagi, M., Imanaka, T. J. Biochem. (1999) [Pubmed]
  28. Properties of exonuclease-resistant, psoralen-conjugated oligodeoxyribonucleotides in vitro and in cell culture. Levis, J.T., Miller, P.S. Antisense Res. Dev. (1994) [Pubmed]
 
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