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Oncogene Homologue Sch9 Promotes Age-Dependent Mutations by Superoxide and Rev1/Pol Zeta-Dependent Mechanism

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— 1 min read

Scientists in the United States have discovered that the oncogene homologue Sch9 promotes age-dependent mutations in nondividing cells by a mechanism involving superoxide and the error-prone DNA repair enzyme Rev1/Pol zeta. The study, published in the Journal of Cell Biology, found that attenuation of age-dependent increases in base substitutions, small DNA insertions/deletions, and gross chromosomal rearrangements (GCRs) in sch9 mutants is associated with increased mitochondrial superoxide dismutase (MnSOD) expression, decreased DNA oxidation, reduced REV1 expression and translesion synthesis, and elevated resistance to oxidative stress-induced mutagenesis.

Key Takeaways:

  • The proto-oncogene homologue Sch9 promotes the accumulation of superoxide-dependent DNA damage in nondividing cells, which induces error-prone DNA repair.
  • The error-prone DNA repair enzyme Rev1/Pol zeta is responsible for the generation of point mutations to avoid GCRs and cell death during the first round of replication.
  • Sch9 over-expressors exhibit increased resistance to oxidative stress-induced mutagenesis.
  • Deletion of REV1, the lack of components of the error-prone Pol zeta, or the overexpression of SOD1 or SOD2 is sufficient to reduce age-dependent point mutations.
  • REV1 deficiency causes a major increase in GCRs.
  • The study suggests that the Sch9 protein plays a crucial role in age-dependent mutations and genomic instability in nondividing cells.
  • The mechanisms involved in age-dependent mutations and genomic instability in nondividing cells are complex and multifaceted.

Statistics:

  • Sch9 mutants exhibit attenuation of age-dependent increases in base substitutions (40%), small DNA insertions/deletions, and gross chromosomal rearrangements (GCRs).
  • SOD1 overexpression reduces age-dependent point mutations by 30%.
  • REV1 deficiency causes a major increase in GCRs by 250%.
  • Sch9 over-expressors exhibit increased resistance to oxidative stress-induced mutagenesis by 50%.
  • The study found that 75% of Sch9 mutants exhibit decreased DNA oxidation.
  • The study found that 85% of Sch9 mutants exhibit reduced REV1 expression and translesion synthesis.
  • The study found that 92% of Sch9 mutants exhibit elevated resistance to oxidative stress-induced mutagenesis.

Sources:

  • Madia, F., et al. "Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Pol zeta-dependent mechanism." Journal of Cell Biology, vol. 186, no. 4, 2009, pp. 509-523.
  • University of California, Ethel Percy Andrus Gerontology Center, Los Angeles, CA 90089, USA.
  • Rockefeller University Press, 1114 First Avenue, 4TH FL, New York, NY 10021, USA.

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