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EXO1  -  Exo1p

Saccharomyces cerevisiae S288c

Synonyms: DHS1, EXO I, Exodeoxyribonuclease 1, Exodeoxyribonuclease I, Exonuclease I, ...
 
 
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Disease relevance of EXO1

 

High impact information on EXO1

  • An exo1 mutant displays a mutator phenotype and alters activity of the ade6-M387 marker effect [3].
  • In the absence of Exo1, telomerase- and recombination-defective yeast can resume cell cycle progression, despite degradation of telomeric regions from many chromosomes [4].
  • EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants [5].
  • We establish that cell cycle arrest of yku70Delta mutants is associated with increasing levels of single-stranded DNA in subtelomeric Y' regions, and find that the mismatch repair-associated EXO1 gene is required for both ssDNA generation and cell cycle arrest of yku70Delta mutants [5].
  • Using the neutral-neutral two-dimensional electrophoresis technique (2D gel) and psoralen crosslinking combined with electron microscopy (EM), we found that the Exo1 exonuclease is recruited to stalled forks and, in rad53 mutants, counteracts reversed fork accumulation by generating ss-DNA intermediates [1].
 

Biological context of EXO1

  • DNA interstrand cross-link repair in the Saccharomyces cerevisiae cell cycle: overlapping roles for PSO2 (SNM1) with MutS factors and EXO1 during S phase [6].
  • Therefore, PSO2, EXO1, and MSH2 also appear to have overlapping roles in the processing of some forms of endogenous DNA damage that occur at an irreversibly collapsed replication fork [6].
  • A search for highly expressed cDNAs that suppress the DNA repair deficiency of rad50 mutants yielded multiple isolates of two genes: EXO1 and TLC1 [7].
  • High-copy plasmids bearing mutations in the conserved EXO1 nuclease domain were unable to suppress msh2-L560S pol3-01 conditional lethality [8].
  • We show that overexpression of EXO1 suppresses multiple rad27 null mutation-associated phenotypes derived from DNA replication defects, including temperature sensitivity, Okazaki fragment accumulation, the rate of minichromosome loss, and an elevated mutation frequency [9].
 

Associations of EXO1 with chemical compounds

  • Multiple copies of the EXO1 gene, encoding a 5' to 3' double-strand DNA exonuclease, were found to suppress the high MMS sensitivity of these mutants [10].
  • The essential role of the invariant glutamate at the Exo1 site was confirmed and the participation of four amino acids (aa) in the 3'-5' Exo function revealed [11].
 

Physical interactions of EXO1

  • However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1 [12].
  • Here we report yeast two-hybrid results suggesting that Exo1p can interact physically with MutLalpha through the Mlh1p subunit [13].
 

Other interactions of EXO1

  • Here we establish a novel overlapping function for PSO2 with MutS mismatch repair factors and the 5'-3' exonuclease Exo1 in the repair of DNA ICLs, which is confined to S phase [6].
  • Using a chromosomally integrated inverted-repeat substrate, we also show that loss of both pso2 and exo1/msh2 reduces spontaneous homologous recombination rates [6].
  • This suggests that other nucleases can compensate for loss of the Exo1 and Mre11 nucleases, but not of the Mre11-Rad50-Xrs2 complex [14].
  • Overlapping functions of the Saccharomyces cerevisiae Mre11, Exo1 and Rad27 nucleases in DNA metabolism [14].
  • The strongest homology to Din7 was found with the Dhs1 protein of S. cerevisiae, the function of which is essentially unknown [15].
 

Analytical, diagnostic and therapeutic context of EXO1

References

  1. Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells. Cotta-Ramusino, C., Fachinetti, D., Lucca, C., Doksani, Y., Lopes, M., Sogo, J., Foiani, M. Mol. Cell (2005) [Pubmed]
  2. Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance. Lee, S.E., Bressan, D.A., Petrini, J.H., Haber, J.E. DNA Repair (Amst.) (2002) [Pubmed]
  3. A role for exonuclease I from S. pombe in mutation avoidance and mismatch correction. Szankasi, P., Smith, G.R. Science (1995) [Pubmed]
  4. Telomerase- and recombination-independent immortalization of budding yeast. Maringele, L., Lydall, D. Genes Dev. (2004) [Pubmed]
  5. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Maringele, L., Lydall, D. Genes Dev. (2002) [Pubmed]
  6. DNA interstrand cross-link repair in the Saccharomyces cerevisiae cell cycle: overlapping roles for PSO2 (SNM1) with MutS factors and EXO1 during S phase. Barber, L.J., Ward, T.A., Hartley, J.A., McHugh, P.J. Mol. Cell. Biol. (2005) [Pubmed]
  7. Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase). Lewis, L.K., Karthikeyan, G., Westmoreland, J.W., Resnick, M.A. Genetics (2002) [Pubmed]
  8. EXO1 and MSH6 are high-copy suppressors of conditional mutations in the MSH2 mismatch repair gene of Saccharomyces cerevisiae. Sokolsky, T., Alani, E. Genetics (2000) [Pubmed]
  9. Complementary functions of the Saccharomyces cerevisiae Rad2 family nucleases in Okazaki fragment maturation, mutation avoidance, and chromosome stability. Sun, X., Thrower, D., Qiu, J., Wu, P., Zheng, L., Zhou, M., Bachant, J., Wilson, D.M., Shen, B. DNA Repair (Amst.) (2003) [Pubmed]
  10. Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae. Tsubouchi, H., Ogawa, H. Mol. Biol. Cell (2000) [Pubmed]
  11. Isolation and characterization of ten mutator alleles of the mitochondrial DNA polymerase-encoding MIP1 gene from Saccharomyces cerevisiae. Hu, J.P., Vanderstraeten, S., Foury, F. Gene (1995) [Pubmed]
  12. Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway. Nakada, D., Hirano, Y., Sugimoto, K. Mol. Cell. Biol. (2004) [Pubmed]
  13. Interactions of Exo1p with components of MutLalpha in Saccharomyces cerevisiae. Tran, P.T., Simon, J.A., Liskay, R.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  14. Overlapping functions of the Saccharomyces cerevisiae Mre11, Exo1 and Rad27 nucleases in DNA metabolism. Moreau, S., Morgan, E.A., Symington, L.S. Genetics (2001) [Pubmed]
  15. Characterization of a novel DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, which is a structural homolog of the RAD2 and RAD27 DNA repair genes. Mieczkowski, P.A., Fikus, M.U., Ciesla, Z. Mol. Gen. Genet. (1997) [Pubmed]
  16. Molecular cloning of a gene, DHS1, which complements a drug-hypersensitive mutation of the yeast Saccharomyces cerevisiae. Lee, Y.S., Shimizu, J., Yoda, K., Yamasaki, M. Biosci. Biotechnol. Biochem. (1994) [Pubmed]
 
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