Mutagen sensitivity and suppression of position-effect variegation result from mutations in mus209, the Drosophila gene encoding PCNA

EMBO J. 1994 Mar 15;13(6):1450-9.

Abstract

The mus209B1 mutant of Drosophila melanogaster exhibits a complex pleiotropy of temperature-sensitive (ts) lethality, hypersensitivity to DNA-damaging agents such as ionizing radiation and methyl methanesulfonate, suppression of position-effect variegation (PEV), and female sterility. Our discovery that mus209 encodes proliferating cell nuclear antigen (PCNA), which is an indispensable component of the DNA replication apparatus, suggests that alterations to chromosome replication may underlie that pleiotropy. Nine lethal mutations, three of them ts, genetically define the Pcna locus. Temperature shift studies reveal that the vital function of PCNA is required throughout virtually all stages of fly development, and that maternally encoded PCNA is essential for embryogenesis. All three ts mutants strongly suppress PEV, which suggests a role for PCNA in chromatin assembly or modification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA
  • DNA Repair
  • Drosophila melanogaster
  • Female
  • Male
  • Methyl Methanesulfonate / toxicity*
  • Molecular Sequence Data
  • Mutagens / toxicity*
  • Mutation*
  • Nuclear Proteins / genetics*
  • Proliferating Cell Nuclear Antigen
  • Radiation Tolerance / genetics
  • Transcription, Genetic

Substances

  • Mutagens
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • DNA
  • Methyl Methanesulfonate