Journal
CANCER RESEARCH
Volume 70, Issue 8, Pages 3189-3198Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-3422
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Funding
- NIH [CA82741]
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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. Cancer Res; 70(8); 3189-98. (C) 2010 AACR.
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