+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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

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

Nucleic Acids Research 44(22): 10879-10897

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.

(PDF emailed within 0-6 h: $19.90)

Accession: 058791965

Download citation: RISBibTeXText

PMID: 27924011

DOI: 10.1093/nar/gkw921

Related references

Differential contributory roles of nucleotide excision and homologous recombination repair for enhancing cisplatin sensitivity in human ovarian cancer cells. Molecular Cancer 10: 24, 2011

Homologous recombination deficiency and ovarian cancer. European Journal of Cancer 60: 49-58, 2017

The roles of homologous recombination and the immune system in the genomic evolution of cancer. Journal of Translational Science 5(2), 2019

Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy. Gynecologic Oncology 137(2): 343-350, 2015

Translational Research Opportunities Regarding Homologous Recombination in Ovarian Cancer. International Journal of Molecular Sciences 19(10), 2018

Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer. Pathology Oncology Research 2019, 2019

Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discovery 5(11): 1137-1154, 2016

Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics 73(Suppl 1): E450s, 2018

Ovarian cancer: Status of homologous recombination pathway as a predictor of drug response. Critical Reviews in Oncology/Hematology 101: 50-59, 2017

Recent Patents for Homologous Recombination Deficiency Assays Among Women with Ovarian Cancer. Recent Patents on Biotechnology 9(2): 86-101, 2016

Genomic signatures as predictive biomarkers of homologous recombination deficiency in ovarian cancer. European Journal of Cancer 86: 5-14, 2017

Development of serous ovarian cancer is associated with the expression of homologous recombination pathway proteins. Pathology Oncology Research 20(4): 931-938, 2015

Progress in the treatment of ovarian cancer-lessons from homologous recombination deficiency-the first 10 years. Annals of Oncology 27 Suppl 1: I1-I3, 2017

Some unsolved problems and unresolved issues in radiation cytogenetics: a review and new data on roles of homologous recombination and non-homologous end joining. Mutation Research 701(1): 12-22, 2010

Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. Gynecologic Oncology Research and Practice 4: 4, 2017