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Updated: Dec 11, 2025

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

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Platinum-Induced Ubiquitination of Phosphorylated H2AX by RING1A Is Mediated by Replication Protein A in Ovarian

Shruthi Sriramkumar1, Timothy D Matthews1, Ahmed H Ghobashi2

  • 1Cell, Molecular and Cancer Biology Graduate Program and Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana.

Molecular Cancer Research : MCR
|August 18, 2020
PubMed

Insights

Platinum resistance in ovarian cancer is linked to DNA repair. The study shows RING1A protein is crucial for repairing platinum DNA damage, suggesting it as a therapeutic target to improve chemotherapy response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Platinum resistance is a major challenge in high-grade serous ovarian cancer treatment.
  • DNA damage response (DDR) pathways, including nucleotide excision repair (NER) and homologous recombination repair (HRR), are activated by platinum agents.
  • Chromatin modifiers, such as polycomb repressive complex 1 (PRC1), are dysregulated in ovarian cancer and may influence platinum resistance.

Purpose of the Study:

  • To investigate the role of chromatin modifiers, specifically PRC1 members, in the DNA damage response to platinum agents in ovarian cancer.
  • To elucidate the mechanism by which RING1A participates in repairing platinum-induced DNA damage.

Main Methods:

  • Utilized ovarian cancer cell lines to study DNA damage response pathways.
  • Investigated the localization and function of RING1A at sites of platinum DNA damage.
  • Assessed the impact of RING1A deficiency on DNA repair, cell cycle checkpoints, and platinum sensitivity.

Main Results:

  • RING1A mediates monoubiquitination of H2AX (γH2AXub1) at platinum DNA damage sites.
  • NER and HRR pathways, along with replication protein A, are involved in RING1A recruitment and γH2AXub1 modification.
  • RING1A deficiency compromises the G2-M DNA damage checkpoint, impairs DNA repair, and enhances platinum sensitivity in ovarian cancer cells.

Conclusions:

  • RING1A plays a critical role in the DNA damage response to platinum chemotherapy in ovarian cancer.
  • Targeting RING1A could be a strategy to overcome platinum resistance and improve treatment outcomes in ovarian cancer patients.

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