The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination

Nucleic Acids Res. 2019 Nov 4;47(19):10151-10165. doi: 10.1093/nar/gkz738.


RAD51 plays a central role in homologous recombination during double-strand break repair and in replication fork dynamics. Misregulation of RAD51 is associated with genetic instability and cancer. RAD51 is regulated by many accessory proteins including the highly conserved Shu complex. Here, we report the function of the human Shu complex during replication to regulate RAD51 recruitment to DNA repair foci and, secondly, during replication fork restart following replication fork stalling. Deletion of the Shu complex members, SWS1 and SWSAP1, using CRISPR/Cas9, renders cells specifically sensitive to the replication fork stalling and collapse caused by methyl methanesulfonate and mitomycin C exposure, a delayed and reduced RAD51 response, and fewer sister chromatid exchanges. Our additional analysis identified SPIDR and PDS5B as novel Shu complex interacting partners and genetically function in the same pathway upon DNA damage. Collectively, our study uncovers a protein complex, which consists of SWS1, SWSAP1, SPIDR and PDS5B, involved in DNA repair and provides insight into Shu complex function and composition.

Publication types

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

MeSH terms

  • CRISPR-Cas Systems / genetics
  • Calcium-Binding Proteins / genetics*
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA Replication / genetics
  • DNA-Binding Proteins / genetics*
  • Genomic Instability / genetics
  • Homologous Recombination / genetics*
  • Humans
  • Multiprotein Complexes / genetics
  • Nuclear Proteins / genetics*
  • Rad51 Recombinase / genetics
  • Rec A Recombinases / genetics*
  • Sister Chromatid Exchange / genetics
  • Transcription Factors / genetics*


  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • EFHD2 protein, human
  • Multiprotein Complexes
  • Nuclear Proteins
  • PDS5B protein, human
  • SPIDR protein, human
  • SWSAP1 protein, human
  • Transcription Factors
  • Rad51 Recombinase
  • Rec A Recombinases