The recombination-deficient mutant RPA (rfa1-t11) is displaced slowly from single-stranded DNA by Rad51 protein

J Biol Chem. 2003 Jun 27;278(26):23410-7. doi: 10.1074/jbc.M302995200. Epub 2003 Apr 14.

Abstract

Replication protein-A (RPA) is involved in many processes of DNA metabolism, including DNA replication, repair, and recombination. Cells carrying a mutation in the largest subunit of RPA (rfa1-t11: K45E) have defects in meiotic recombination, mating-type switching, and survival after DNA damage caused by UV and methyl methanesulfonate, as well as increased genome instability; however, this mutant has no significant defect in DNA replication. We purified the RPA heterotrimer containing the rfa1-t11 substitution (RPA(rfa1-t11)). This mutant RPA binds single-stranded DNA (ssDNA) with the same site size, and the RPA(rfa1-t11).ssDNA complex shows a similar sensitivity to disruption by salt as the wild-type RPA.ssDNA complex. RPA(rfa1-t11) stimulates DNA strand exchange, provided that the Rad51 protein.ssDNA nucleoprotein complex is assembled prior to introduction of the mutant RPA. However, RPA(rfa1-t11) is displaced from ssDNA by Rad51 protein more slowly than wild-type RPA and, as a consequence, Rad51 protein-mediated DNA strand exchange is inhibited when the ssDNA is in a complex with RPA(rfa1-t11). Rad52 protein can stimulate displacement of RPA(rfa1-t11) from ssDNA by Rad51 protein, but the rate of displacement remains slow compared with wild-type RPA. These in vitro results suggest that, in vivo, RPA is bound to ssDNA prior to Rad51 protein and that RPA displacement by Rad51 protein is a critical step in homologous recombination, which is impaired in the rfa1-t11 mutation.

Publication types

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

MeSH terms

  • Binding, Competitive
  • DNA, Single-Stranded / metabolism*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / pharmacology
  • Dose-Response Relationship, Drug
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Kinetics
  • Models, Biological
  • Mutation*
  • Nucleoproteins / metabolism
  • Rad51 Recombinase
  • Recombination, Genetic / genetics*
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / pharmacology
  • Salts / pharmacology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology

Substances

  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Fungal Proteins
  • Nucleoproteins
  • RFA1 protein, S cerevisiae
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • Salts
  • Transcription Factors
  • Rad51 Recombinase