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A more recent version of this article appeared on June 29, 2001
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M101032200v1
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Papers In Press, published online ahead of print May 15, 2001
J. Biol. Chem, 10.1074/jbc.M101032200
Submitted on February 2, 2001
Revised on May 11, 2001
Accepted on May 14, 2001

DNA Repair Excision Nuclease Attacks Undamaged DNA: A Potential Source of Spontaneous Mutations

Mark E. Branum, Joyce T. Reardon, and Aziz Sancar

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260

Corresponding Author: Aziz_Sancar{at}med.unc.edu

Nucleotide excision repair is a general repair system which eliminates many dissimilar lesions from DNA. In an effort to understand substrate determinants of this repair system we tested DNAs with minor backbone modifications using the ultrasensitive excision assay. We found that a phosphorothioate and a methylphosphonate were excised with low efficiency. Surprisingly, we also found that fragments of 23-28 nucleotides and of 12-13 nucleotides characteristic of human and E. coli excision repair, respectively, were removed from undamaged DNA at a significant rate. Considering the relative abundance of undamaged DNA in comparison to damaged DNA in the course of the life of an organism we conclude that, in general, excision from and resynthesis of undamaged DNA may exceed the excision and resynthesis caused by DNA damage. As resynthesis is invariably associated with mutations we propose that gratuitous repair may be an important source of spontaneous mutations.


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