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

This Article Full Text (PDF) 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 Burger, R. M. Articles by Birdsall, B. Search for Related Content PubMed PubMed Citation Articles by Burger, R. M. Articles by Birdsall, B. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 269, Issue 42, 25978-25985, 10, 1994

The DNA cleavage pathway of iron bleomycin. Strand scission precedes deoxyribose 3-phosphate bond cleavage

RM Burger, K Drlica and B Birdsall
Public Health Research Institute, New York, New York 10016.

DNA strand scission initiated by bleomycin is a multistep process. Three C-C or C-O bonds are broken, releasing base propenal, a nucleic base derivative with deoxyribose carbons 1-3. Either C-3'-(phosphate-O) cleavage or C-3'-C-4' plus C-1'-(ring-O) bond cleavages could cause strand cleavage. To determine the sequence of bond breakage, d(CAAGCTTG) duplex was examined for rates of 1) strand scission, monitored by the hyperchromicity of cleavage-induced denaturation; 2) base propenal formation, monitored by 1H NMR spectroscopy; 3) 5'- terminal phosphomonoester formation, monitored by 31P NMR spectroscopy. Strand scission occurred with t 1/2 = 4.1 +/- 0.5 min at 4 degrees C, faster than base propenal formation (t 1/2 = 6.7 +/- 0.3 min). Thus newly cleaved DNA includes a base propenal precursor (t 1/2 = 2-3 min). The 5'-phosphate terminus forms (t 1/2 = 7.4 +/- 0.8 min) concurrently with base propenal. Since strand scission precedes phosphomonoester formation, strand scission cannot arise from C-3'-(phosphate-O) cleavage. Instead, the base propenal precursor must be linked to the future 5'-phosphate terminus, with strand scission arising from a combination of C-3'-C-4' and C-1'-(ring-O) bond cleavages. These results provide experimental support for a recently proposed mechanism that accommodates an early oxygen attack at C-4' and 2'-deprotonation without requiring simultaneous strand scission and 5'-phosphate terminus formation.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Chen, M. K. Ghorai, G. Kenney, and J. Stubbe Mechanistic studies on bleomycin-mediated DNA damage: multiple binding modes can result in double-stranded DNA cleavage Nucleic Acids Res., June 1, 2008; 36(11): 3781 - 3790. [Abstract] [Full Text] [PDF]

				M. L. Hornback and R. M. Roop II The Brucella abortus xthA-1 Gene Product Participates in Base Excision Repair and Resistance to Oxidative Killing but Is Not Required for Wild-Type Virulence in the Mouse Model J. Bacteriol., February 15, 2006; 188(4): 1295 - 1300. [Abstract] [Full Text] [PDF]

				H.-D. Junker, S. T. Hoehn, R. C. Bunt, V. Marathius, J. Chen, C. J. Turner, and J. Stubbe Synthesis, characterization and solution structure of tethered oligonucleotides containing an internal 3'-phosphoglycolate, 5'-phosphate gapped lesion Nucleic Acids Res., December 15, 2002; 30(24): 5497 - 5508. [Abstract] [Full Text] [PDF]

				A. Harsch, L. A. Marzilli, R. C. Bunt, J. Stubbe, and P. Vouros Accurate and rapid modeling of iron-bleomycin-induced DNA damage using tethered duplex oligonucleotides and electrospray ionization ion trap mass spectrometric analysis Nucleic Acids Res., May 1, 2000; 28(9): 1978 - 1985. [Abstract] [Full Text] [PDF]

				S. Srivastava, A. Chandra, L.-F. Wang, W. E. Seifert Jr., B. B. DaGue, N. H. Ansari, S. K. Srivastava, and A. Bhatnagar Metabolism of the Lipid Peroxidation Product, 4-Hydroxy-trans-2-nonenal, in Isolated Perfused Rat Heart J. Biol. Chem., May 1, 1998; 273(18): 10893 - 10900. [Abstract] [Full Text] [PDF]