Targeted inhibition of replication protein A reveals cytotoxic activity, synergy with chemotherapeutic DNA-damaging agents, and insight into cellular function

Sarah C. Shuck, John J. Turchi

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Targeting uncontrolled cell proliferation and resistance to DNA-damaging chemotherapeutics with a single agent has significant potential in cancer treatment. Replication protein A (RPA), the eukaryotic ssDNA-binding protein, is essential for genomic maintenance and stability via roles in both DNA replication and repair. We have identified a novel small molecule that inhibits the in vitro and cellular ssDNA-binding activity of RPA, prevents cell cycle progression, induces cytotoxicity, and increases the efficacy of chemotherapeutic DNA-damaging agents. These results provide new insight into the mechanism of RPA-ssDNA interactions in chromosome maintenance and stability. This represents the first molecularly targeted eukaryotic DNA-binding inhibitor and reveals the utility of targeting a protein-DNA interaction as a therapeutic strategy for cancer treatment. (c)2010 AACR.

Original languageEnglish (US)
Pages (from-to)3789-3798
Number of pages10
JournalCancer Research
Volume70
Issue number8
DOIs
StatePublished - Apr 15 2010

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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