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    Proc Natl Acad Sci U S A. 2002 May 14;99(10):6673-8.

    Preferential binding of ATR protein to UV-damaged DNA.

    Unsal-Kaçmaz K, Makhov AM, Griffith JD, Sancar A.

    Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

    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.

    PMID: 12011431 [PubMed - indexed for MEDLINE]

    PMCID: 124461

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