Preferential binding of ATR protein to UV-damaged DNA
- Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599
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Communicated by Thomas D. Petes, University of North Carolina, Chapel Hill, NC (received for review February 14, 2002)
Abstract
The ATR protein is a member of the phosphoinositide 3-kinase-related kinase family and plays an important role in UV-induced DNA damage checkpoint response. Its role as a signal transducer in cell cycle checkpoint is well established, but it is currently unclear whether ATR functions as a damage sensor as well. Here we have purified the ATR protein and investigated its interaction with DNA by using biochemical analysis and electron microscopy. We find that ATR is a DNA-binding protein with higher affinity to UV-damaged than undamaged DNA. In addition, damaged DNA stimulates the kinase activity of ATR to a significantly higher level than undamaged DNA. Our data suggest that ATR may function as an initial sensor in the DNA damage checkpoint response.
Footnotes
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↵ * To whom reprint requests should be addressed at: Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599. E-mail: Aziz_Sancar{at}med.unc.edu.
- Abbreviations:
- PIKK,
- phosphoinositide 3-kinase-related kinase;
- DNA-PK,
- DNA-dependent protein kinase;
- RFC,
- Replication Factor C;
- HEK,
- human embryonic kidney
- Copyright © 2002, The National Academy of Sciences
