HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 16, 13666-13672, April 19, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/16/13666    most recent M200209200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pommier, Y. Articles by Jerina, D. M. Search for Related Content PubMed PubMed Citation Articles by Pommier, Y. Articles by Jerina, D. M.

Different Effects on Human Topoisomerase I by Minor Groove and Intercalated Deoxyguanosine Adducts Derived from Two Polycyclic Aromatic Hydrocarbon Diol Epoxides at or Near a Normal Cleavage Site^*

Yves Pommier^§, Glenda Kohlhagen, Gary S. Laco, Heiko Kroth^¶, Jane M. Sayer^¶, and Donald M. Jerina^¶

From the  Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, and the ^¶ Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892

Topoisomerase I (top1) relieves supercoiling in DNA by forming transient covalent cleavage complexes. These cleavage complexes can accumulate in the presence of damaged DNA or anticancer drugs that either intercalate or lie in the minor groove. Recently we reported that covalent diol epoxide (DE) adducts of benzo[a]pyrene (BaP) at the exocyclic amino group of G(+1) block cleavage at a preferred cleavage site (~CTTG(+1)G(+2)A~) and cause accumulation of cleavage products at remote sites. In the present study, we have found that the 10S G(+2) adduct of BaP DE, which lies toward the scissile bond in the minor groove, blocks normal cleavage, whereas the 10R isomer, which orients away from this bond, allows normal cleavage but blocks religation. In contrast to BaP, the pair of benzo[c] phenanthrene (BcPh) DE adducts at G(+2), which intercalate from the minor groove either between G(+1)/G(+2) or between G(+2)/A, allow normal cleavage but block religation. Both intercalated BcPh DE adducts at G(+1) suppress normal cleavage, as do both groove bound BaP DE adducts at this position. These studies demonstrate that these DE adducts provide a novel set of tools to study DNA topoisomerases and emphasize the importance of contacts between the minor groove and top1's catalytic site.

This article has been cited by other articles:

				A. A. Johnson, J. M. Sayer, H. Yagi, S. S. Patil, F. Debart, M. A. Maier, D. R. Corey, J.-J. Vasseur, T. R. Burke Jr., V. E. Marquez, et al. Effect of DNA Modifications on DNA Processing by HIV-1 Integrase and Inhibitor Binding: ROLE OF DNA BACKBONE FLEXIBILITY AND AN OPEN CATALYTIC SITE J. Biol. Chem., October 27, 2006; 281(43): 32428 - 32438. [Abstract] [Full Text] [PDF]

				Z.-H. Miao, V. A. Rao, K. Agama, S. Antony, K. W. Kohn, and Y. Pommier 4-Nitroquinoline-1-Oxide Induces the Formation of Cellular Topoisomerase I-DNA Cleavage Complexes. Cancer Res., July 1, 2006; 66(13): 6540 - 6545. [Abstract] [Full Text] [PDF]

				C. Marchand, S. Antony, K. W. Kohn, M. Cushman, A. Ioanoviciu, B. L. Staker, A. B. Burgin, L. Stewart, and Y. Pommier A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex. Mol. Cancer Ther., February 1, 2006; 5(2): 287 - 295. [Abstract] [Full Text] [PDF]

				Z.-Y. Liao, O. Sordet, H.-L. Zhang, G. Kohlhagen, S. Antony, W. H. Gmeiner, and Y. Pommier A Novel Polypyrimidine Antitumor Agent FdUMP[10] Induces Thymineless Death with Topoisomerase I-DNA Complexes Cancer Res., June 1, 2005; 65(11): 4844 - 4851. [Abstract] [Full Text] [PDF]

				S. Antony, J. A. Theruvathu, P. J. Brooks, D.-T. Lesher, M. Redinbo, and Y. Pommier Enhancement of camptothecin-induced topoisomerase I cleavage complexes by the acetaldehyde adduct N2-ethyl-2'-deoxyguanosine Nucleic Acids Res., October 21, 2004; 32(18): 5685 - 5692. [Abstract] [Full Text] [PDF]

				A. A. Johnson, J. M. Sayer, H. Yagi, G. P. Kalena, R. Amin, D. M. Jerina, and Y. Pommier Position-specific Suppression and Enhancement of HIV-1 Integrase Reactions by Minor Groove Benzo[a]pyrene Diol Epoxide Deoxyguanine Adducts: IMPLICATIONS FOR MOLECULAR INTERACTIONS BETWEEN INTEGRASE AND DNA SUBSTRATES J. Biol. Chem., February 27, 2004; 279(9): 7947 - 7955. [Abstract] [Full Text] [PDF]

				Q. A. Khan, G. Kohlhagen, R. Marshall, C. A. Austin, G. P. Kalena, H. Kroth, J. M. Sayer, D. M. Jerina, and Y. Pommier Position-specific trapping of topoisomerase II by benzo[a]pyrene diol epoxide adducts: Implications for interactions with intercalating anticancer agents PNAS, October 14, 2003; 100(21): 12498 - 12503. [Abstract] [Full Text] [PDF]

				T. Furuta, H. Takemura, Z.-Y. Liao, G. J. Aune, C. Redon, O. A. Sedelnikova, D. R. Pilch, E. P. Rogakou, A. Celeste, H. T. Chen, et al. Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage Complexes J. Biol. Chem., May 23, 2003; 278(22): 20303 - 20312. [Abstract] [Full Text] [PDF]

				L. Tian, J. M. Sayer, H. Kroth, G. Kalena, D. M. Jerina, and S. Shuman Benzo[a]pyrene-dG Adduct Interference Illuminates the Interface of Vaccinia Topoisomerase with the DNA Minor Groove J. Biol. Chem., March 7, 2003; 278(11): 9905 - 9911. [Abstract] [Full Text] [PDF]