hSWS1·SWSAP1 is an evolutionarily conserved complex required for efficient homologous recombination repair

J Biol Chem. 2011 Dec 2;286(48):41758-66. doi: 10.1074/jbc.M111.271080. Epub 2011 Sep 29.

Abstract

The Shu complex in yeast plays an important role in the homologous recombination pathway, which is critical for the maintenance of genomic integrity. The identification of human SWS1 (hSWS1) as the homolog of budding yeast Shu2 implicated that the Shu complex is evolutionarily conserved. However, the human counterparts of other components in this complex have not yet been identified and characterized. Here we describe the characterization of a novel human component of this complex, SWSAP1 (hSWS1-associated protein 1)/C19orf39. We show that hSWS1 and SWSAP1 form a stable complex in vivo and in vitro. hSWS1 and SWSAP1 are mutually interdependent for their stability. We further demonstrate that the purified hSWS1·SWSAP1 complex possesses single-stranded DNA-binding activity and DNA-stimulated ATPase activity. Moreover, SWSAP1 interacts with RAD51 and RAD51 paralogs, and depletion of SWSAP1 causes defects in homologous recombination repair. Thus, our results suggest that the human Shu complex (hSWS1·SWSAP1) has an evolutionarily conserved function in homologous recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Evolution, Molecular*
  • HeLa Cells
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Recombinational DNA Repair / physiology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism

Substances

  • Calcium-Binding Proteins
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • EFHD2 protein, human
  • Multiprotein Complexes
  • RAD51 protein, human
  • Rad51 Recombinase