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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
23
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pubmed:dateCreated |
1994-7-21
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pubmed:abstractText |
Soluble extracts of human cells repair gamma-ray-induced single-strand breaks in DNA. Accompanying NAD-dependent automodification of poly(ADP-ribose) polymerase is required for effective DNA rejoining. The kinetics of poly(ADP-ribose) synthesis by this polymerase, and subsequent polymer degradation by poly(ADP-ribose) glycohydrolase, have been compared with the rate of DNA repair. The results agree with previous in vivo data. In response to addition of gamma-irradiated plasmid DNA, rapid and heavy automodification of poly(ADP-ribose) polymerase occurred in NAD-containing human cell extracts. After 2 min at 30 degrees C, when very little DNA rejoining had yet occurred, synthesis of long polymers essentially ceased, although only a minor fraction of the NAD had been consumed. Poly(ADP-ribose) chains were then reduced to oligomer size by poly(ADP-ribose) glycohydrolase. These short chains were present for longer times and were sufficient to permit DNA repair. Thus, most but not all poly(ADP-ribose) synthesis could be suppressed without marked inhibition of DNA repair, and prolonged occurrence of long poly(ADP-ribose) chains in consequence to glycohydrolase inhibition did not improve DNA repair. The temporary presence of short poly(ADP-ribose) chains on poly(ADP-ribose) polymerase avoids inhibition of excision-repair by that protein, but the initial very transient formation of long and branched chains of poly(ADP-ribose) in response to DNA damage apparently serves an entirely different purpose. Local poly(ADP-ribose) synthesis in the vicinity of a DNA strand interruption causes negative charge repulsion, and this may function to prevent accidental homologous recombination events within tandem repeat DNA sequences.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
14
|
pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7099-106
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading | |
pubmed:year |
1994
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pubmed:articleTitle |
Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage.
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pubmed:affiliation |
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, U.K.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|