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RPS15 Coordinates with CtIP to Facilitate Homologous Recombination and Confer Therapeutic Resistance in Breast Cancer

Baohang Lin1,2, Guan Huang3, Zishan Yuan2

  • 1Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.

Radiation Research
|October 3, 2024
PubMed

Insights

RPS15 protein promotes DNA repair by aiding homologous recombination, a crucial process for genome stability. This discovery suggests RPS15 as a potential target for cancer therapies.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • DNA double-strand breaks (DSBs) threaten genome stability.
  • Homologous recombination (HR) is a critical repair pathway for DSBs.
  • RNA binding proteins (RBPs) regulate DNA repair, but their roles are not fully understood.

Purpose of the Study:

  • To investigate the role of RPS15, an RBP, in homologous recombination repair.
  • To elucidate the molecular mechanisms by which RPS15 influences HR.
  • To assess the therapeutic potential of targeting RPS15 in cancer treatment.

Main Methods:

  • Investigated RPS15 function in DNA repair.
  • Identified protein-protein interactions using co-immunoprecipitation.
  • Assessed the impact of RPS15 suppression on cancer cell sensitivity to genotoxic agents and PARP1 inhibitors.

Main Results:

  • RPS15 promotes DNA end resection, a key step in HR.
  • RPS15 interacts with CtIP, facilitating CtIP recruitment to DSB sites.
  • RPS15 is essential for RPA coating and RAD51 replacement during HR.
  • Suppression of RPS15 sensitizes cancer cells to X-ray radiation and PARP1 inhibitors.

Conclusions:

  • RPS15 plays a vital role in promoting efficient homologous recombination repair.
  • The RPS15-CtIP interaction is crucial for HR pathway activation.
  • RPS15 represents a potential therapeutic target for enhancing cancer treatment efficacy.

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