期刊
ONCOTARGET
卷 8, 期 25, 页码 40804-40816出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17254
关键词
DNA damage; DNA polymerization; chemotherapy; nucleoside analogs; leukemia
资金
- Department of Defense [W81XWH-13-1-0238]
- Cleveland State University (Faculty Innovation Award)
- Cleveland State University (Summer Undergraduate Research Program)
- Glide Innovation Fund
- Ohio Third Frontier Foundation
Anti-cancer agents exert therapeutic effects by damaging DNA. Unfortunately, DNA polymerases can effectively replicate the formed DNA lesions to cause drug resistance and create more aggressive cancers. To understand this process at the cellular level, we developed an artificial nucleoside that visualizes the replication of damaged DNA to identify cells that acquire drug resistance through this mechanism. Visualization is achieved using click chemistry to covalently attach azide-containing fluorophores to the ethynyl group present on the nucleoside analog after its incorporation opposite damaged DNA. Flow cytometry and microscopy techniques demonstrate that the extent of nucleotide incorporation into genomic DNA is enhanced by treatment with DNA damaging agents. In addition, this nucleoside analog inhibits translesion DNA synthesis and synergizes the therapeutic activity of certain anticancer agents such as temozolomide. The combined diagnostic and therapeutic activities of this synthetic nucleoside analog represent a new paradigm in personalized medicine.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据