The role of the human SWI5-MEI5 complex in homologous recombination repair

J Biol Chem. 2011 Mar 18;286(11):9888-93. doi: 10.1074/jbc.M110.207290. Epub 2011 Jan 20.

Abstract

The Swi5-Mei5 complex and its homologues are involved in specialized recombination pathways in budding and fission yeasts. Although the fission yeast homologue Swi5-Sfr1 is critical for homologous recombination repair, the budding yeast counterpart Sae3-Mei5 is meiosis-specific, interacts with Dmc1, and promotes assembly of Dmc1 on meiotic chromosomes. Here, we identify and characterize the human SWI5-MEI5 (C9orf119-C10orf78) complex. We showed that SWI5 and MEI5 form a stable complex in vitro and in vivo. The C-terminal Swi5 domain of SWI5 and the middle coiled-coil region of MEI5 dictate this conserved interaction. In addition, SWI5-MEI5 directly interacts with RAD51 in vitro. Depletion of SWI5 or MEI5 in human cells causes defects in homologous recombination repair. Finally, SWI5- or MEI5-depleted cells display enhanced sensitivity to ionizing radiation, consistent with the role of this complex in HR repair. Our results suggest that human SWI5-MEI5 has an evolutionarily conserved function in homologous recombination repair.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Repair / physiology*
  • DNA Repair / radiation effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Evolution, Molecular
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Radiation Tolerance / physiology
  • Radiation Tolerance / radiation effects
  • Radiation, Ionizing
  • Recombination, Genetic / physiology*
  • Recombination, Genetic / radiation effects
  • Transcription Factors

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SFR1 protein, human
  • Swi5 protein, human
  • Transcription Factors
  • DMC1 protein, human