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J. Biol. Chem., Vol. 276, Issue 27, 25421-25426, July 6, 2001
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From the Department of Biochemistry and Biophysics,
University of North Carolina School of Medicine, Chapel Hill, North
Carolina 27599
Nucleotide excision repair is a general repair
system that 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 Escherichia 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.
DNA Repair Excision Nuclease Attacks Undamaged DNA
A POTENTIAL SOURCE OF SPONTANEOUS MUTATIONS*
*
This work was supported by National Institutes of Health
Grant GM32833.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry
and Biophysics, Mary Ellen Jones Bldg., CB#7260, University of North
Carolina School of Medicine, Chapel Hill, NC 27599-7260. Tel.:
919-962-0115; Fax: 919-843-8627; E-mail:
Aziz_Sancar@med.unc.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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