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repair of thymine glycol by hnth1 and hneil1 is modulated by base pairing and cis–trans epimerization论文.pdf

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repair of thymine glycol by hnth1 and hneil1 is modulated by base pairing and cis–trans epimerization论文.pdf

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文档介绍:dna repair 5 (2006) 444–454
available at
journal homepage:
Repair of thymine glycol by hNth1 and hNeil1
is modulated by base pairing and
cis–trans epimerization
Maria T. Ocampo-Hafalla a, Alvin Altamirano b, Ashis K. Basu b,
Michael K. Chan a, Jose Eliseo A. Ocampo a, Archie Cummings Jr. a,
Robert J. Boorstein a, Richard P. Cunningham c, George W. Teebor a,∗
a Department of Pathology, New York University Medical Center, New York, NY 10016, USA
b Department of Chemistry, University of Connecticut, Storrs, CT 06269, USA
c Department of Biological Sciences, The University at Albany, State University of New York, NY 12222, USA
article info abstract
Article history: Oxidation of thymine yields 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol. Tg) which,
Received 18 July 2005 as cis 5S,6R and 5R,6S 2’-deoxyribonucleoside diastereoisomers (dTg1, dTg2), are in equilib-
Received in revised form 8 rium with their trans 5S,6S and 5R,6R epimers. The stereoselective excision of Tg from DNA
December 2005 by the mammalian orthologs of E. coli DNA N-glycosylase/AP lyases Nth and Nei was reported
Accepted 12 December 2005 using substrates in which Tg opposed adenine. Since we showed that Tg is the major product
Published on line 30 January 2006 of oxidation of 5-methylcytosine, we asked if the opposing purine influenced stereospecific
enzymatic excision. The human ortholog hNth1 released Tg2 much more rapidly than Tg1
Keywords: regardless of the opposi