Document Detail

Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts.
MedLine Citation:
PMID:  7991608     Owner:  NLM     Status:  MEDLINE    
Nucleotide-excision repair is the repair system for removing bulky lesions from DNA. Humans deficient in this repair pathway suffer from xeroderma pigmentosum (XP), a disease characterized by photodermatoses, including skin cancers. At the cellular level, XP patients fail to remove cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts induced by UV light, as well as other bulky DNA lesions caused by various genotoxic agents. XP cells are not particularly sensitive to ionizing radiation or to alkylating agents that cause mostly nonbulky DNA lesions. Therefore, it has generally been assumed that the human nucleotide-excision repair enzyme (excinuclease) is specific for bulky adducts. To determine the substrate range of human excinuclease we used the highly sensitive excision assay and tested bulky adducts, synthetic apurinic/apyrimidinic sites, N6-methyladenine, O6-methylguanine, and mismatches as potential substrates. We found that all of these "lesions" were removed by human excinuclease, although with vastly different efficiencies.
J C Huang; D S Hsu; A Kazantsev; A Sancar
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  91     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-01-11     Completed Date:  1995-01-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  12213-7     Citation Subset:  IM    
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599.
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MeSH Terms
Base Composition
Base Sequence
CHO Cells
Cell-Free System
DNA Damage*
DNA Repair*
Endodeoxyribonucleases / metabolism*
Escherichia coli / enzymology
Escherichia coli Proteins*
Hela Cells
Molecular Sequence Data
Oligodeoxyribonucleotides / metabolism*
Substrate Specificity
Xeroderma Pigmentosum / enzymology,  physiopathology
Grant Support
Reg. No./Substance:
0/Escherichia coli Proteins; 0/Oligodeoxyribonucleotides; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.25.-/endodeoxyribonuclease uvrABC

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