View : 94 Download: 15

Biochemical basis of genotoxicity of heterocyclic arylamine food mutagens: Human DNA polymerase η selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site

Title
Biochemical basis of genotoxicity of heterocyclic arylamine food mutagens: Human DNA polymerase η selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site
Authors
Choi J.-Y.Stover J.S.Angel K.C.Chowdhury G.Rizzo C.J.Guengerich F.P.
Ewha Authors
최정윤
Issue Date
2006
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 281, no. 35, pp. 25297 - 25306
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Heterocyclic arylamines are highly mutagenic and cause tumors in animal models. The mutagenicity is attributed to the C8- and N2-G adducts, the latter of which accumulates due to slower repair. The C 8- and N2-G adducts derived from 2-amino-3- methylimidazo[4,5-f ]quinoline (IQ) were placed at the G1 and G 3 sites of the NarI sequence, in which the G3 site is an established hot spot for frameshift mutation with the model arylamine derivative 2-acetylaminofluorene but G1 is not. Human DNA polymerase (pol) η extended primers beyond template G-IQ adducts better than did pol κ and much better than pol ι or δ. In 1-base incorporation studies, pol η inserted C and A, pol ι inserted T, and pol κ inserted G. Steady-state kinetic parameters were measured for these dNTPs opposite the C8- and N2-IQ adducts at both sites, being most favorable for pol η. Mass spectrometry of pol η extension products revealed a single major product in each of four cases; with the G1 and G 3 C8-IQ adducts, incorporation was largely error-free. With the G3 N2-IQ adduct, a -2 deletion occurred at the site of the adduct. With the G1 N2-IQ adduct, the product was error-free at the site opposite the base and then stalled. Thus, the pol η products yielded frameshifts with the N2 but not the C 8 IQ adducts. We show a role for pol η and the complexity of different chemical adducts of IQ, DNA position, and DNA polymerases. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M605699200
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
biochemical basis.pdf(540.49 kB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE