Roles for APRIN (PDS5B) in homologous recombination and in ovarian cancer prediction

Couturier, A.M., Fleury, H., Patenaude, A.M., Bentley, V.L., Rodrigue, A., Coulombe, Y., Niraj, J., Pauty, J., Berman, J.N., Dellaire, G., Di Noia, J.M., Mes-Masson, A.M., Masson, J.Y.
Nucleic acids research   44(22): 10879-10897 (Journal)
Registered Authors
Bentley, Victoria, Berman, Jason
brca2 protein, complement factor b, dna, dna damage, dna repair, embryo, fluorescent antibody technique, tumor suppressor genes, lasers, recombination, genetic, zebrafish, ovarian cancer, affinity, olaparib, poly(adp-ribose) polymerase inhibitors, nonhomologous dna end joining, binding (molecular function), palb2 gene
MeSH Terms
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents/pharmacology
  • BRCA2 Protein/metabolism
  • Benzimidazoles/pharmacology
  • Biomarkers, Tumor/chemistry
  • Biomarkers, Tumor/physiology*
  • Cell Line, Tumor
  • DNA Damage
  • DNA-Binding Proteins/chemistry
  • DNA-Binding Proteins/physiology*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Nuclear Proteins/metabolism
  • Ovarian Neoplasms/diagnosis
  • Ovarian Neoplasms/drug therapy
  • Ovarian Neoplasms/metabolism*
  • Ovarian Neoplasms/mortality
  • Phthalazines/pharmacology
  • Piperazines/pharmacology
  • Protein Binding
  • Protein Transport
  • ROC Curve
  • Rad51 Recombinase/metabolism
  • Recombinational DNA Repair
  • Squamous Intraepithelial Lesions of the Cervix/diagnosis
  • Squamous Intraepithelial Lesions of the Cervix/drug therapy
  • Squamous Intraepithelial Lesions of the Cervix/metabolism*
  • Squamous Intraepithelial Lesions of the Cervix/mortality
  • Transcription Factors/chemistry
  • Transcription Factors/physiology*
  • Tumor Suppressor Proteins/metabolism
  • Xenograft Model Antitumor Assays
  • Zebrafish
27924011 Full text @ Nucleic Acids Res.
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA. We show that APRIN strongly improves the annealing of complementary-strand DNA and that it can stimulate this process in synergy with BRCA2. Unlike cohesin constituents, its depletion has no impact on class switch recombination, supporting a specific role for this protein in HR. Furthermore, we show that low APRIN expression levels correlate with a better survival in ovarian cancer patients and that APRIN depletion sensitizes cells to the PARP inhibitor Olaparib in xenografted zebrafish. Our findings establish APRIN as an important and specific actor of HR, with cohesin-independent functions.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes