Suppression of chromosome instability by targeting a DNA helicase in budding yeast

Mol Biol Cell. 2023 Jan 1;34(1):ar3. doi: 10.1091/mbc.E22-09-0395. Epub 2022 Nov 9.

Abstract

Chromosome instability (CIN) is an important driver of cancer initiation, progression, drug resistance, and aging. As such, genes whose inhibition suppresses CIN are potential therapeutic targets. We report here that deletion of an accessory DNA helicase, Rrm3, suppresses high CIN caused by a wide range of genetic or pharmacological perturbations in yeast. Although this helicase mutant has altered cell cycle dynamics, suppression of CIN by rrm3∆ is independent of the DNA damage and spindle assembly checkpoints. Instead, the rrm3∆ mutant may have increased kinetochore-microtubule error correction due to an altered localization of Aurora B kinase and associated phosphatase, PP2A-Rts1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Chromosomal Instability
  • Chromosome Segregation
  • DNA Helicases* / genetics
  • DNA Helicases* / metabolism
  • Kinetochores / metabolism
  • M Phase Cell Cycle Checkpoints
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism

Substances

  • Cell Cycle Proteins
  • DNA Helicases
  • Rrm3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins