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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
42
|
| pubmed:dateCreated |
1994-11-22
|
| pubmed:abstractText |
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.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
21
|
| pubmed:volume |
269
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
25978-85
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading | |
| pubmed:year |
1994
|
| pubmed:articleTitle |
The DNA cleavage pathway of iron bleomycin. Strand scission precedes deoxyribose 3-phosphate bond cleavage.
|
| pubmed:affiliation |
Public Health Research Institute, New York, New York 10016.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|