Related Experiment Video

Updated: Jul 10, 2025

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
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Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

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STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition

Jie Zhou1,2, Run-Cong Nie3, Zhang-Ping He4

  • 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 21, 2023
PubMed

Insights

Stromal antigen 2 (STAG2) deficiency increases DNA damage by impairing homologous recombination (HR) repair. This finding reveals STAG2 as a potential therapeutic target for cancer treatment.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Stromal antigen 2 (STAG2) is a key component of the cohesin complex, frequently mutated in various cancers.
  • The precise function of STAG2 in DNA repair pathways and its therapeutic relevance remain largely unexplored.

Purpose of the Study:

  • To investigate the role of STAG2 in DNA repair mechanisms, specifically homologous recombination (HR).
  • To explore the therapeutic implications of STAG2 deficiency in cancer treatment.

Main Methods:

  • Gene knockout studies to assess the impact of STAG2 deficiency on DNA repair.
  • Analysis of double-stranded breaks (DSBs) and chromosomal aberrations.
  • Evaluation of sensitivity to DNA repair inhibitors (ATMi, PARPi).
  • Chromatin immunoprecipitation assays to study protein recruitment.

Main Results:

  • STAG2 knockout leads to increased DSBs and chromosomal aberrations due to reduced HR repair.
  • STAG2-deficient cells exhibit hypersensitivity to ATMi and PARPi inhibitors.
  • Impaired HR in STAG2-deficient cells is linked to KMT5A-mediated H4K20me1, which reduces BRCA1-BARD1 recruitment.
  • Elevated STAG2 expression correlates with poor cancer patient prognosis.

Conclusions:

  • STAG2 is a critical regulator of homologous recombination repair.
  • Targeting STAG2-mutant tumors with DNA repair inhibitors presents a promising therapeutic strategy.
Keywords:
ATM inhibitorsPARP inhibitorsSTAG2homologous recombinationsynthetic lethality

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