| pubmed-article:18495665 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C0035687 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C0001752 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C0012920 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C0032403 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C1419989 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C1145667 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C1521761 | lld:lifeskim |
| pubmed-article:18495665 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:18495665 | pubmed:issue | 29 | lld:pubmed |
| pubmed-article:18495665 | pubmed:dateCreated | 2008-7-14 | lld:pubmed |
| pubmed-article:18495665 | pubmed:abstractText | Human DNA topoisomerase I plays a dual role in transcription, by controlling DNA supercoiling and by acting as a specific kinase for the SR-protein family of splicing factors. The two activities are mutually exclusive, but the identity of the molecular switch is unknown. Here we identify poly(ADP-ribose) as a physiological regulator of the two topoisomerase I functions. We found that, in the presence of both DNA and the alternative splicing factor/splicing factor 2 (ASF/SF2, a prototypical SR-protein), poly(ADP-ribose) affected topoisomerase I substrate selection and gradually shifted enzyme activity from protein phosphorylation to DNA cleavage. A likely mechanistic explanation was offered by the discovery that poly(ADP-ribose) forms a high affinity complex with ASF/SF2 thereby leaving topoisomerase I available for directing its action onto DNA. We identified two functionally important domains, RRM1 and RS, as specific poly(ADP-ribose) binding targets. Two independent lines of evidence emphasize the potential biological relevance of our findings: (i) in HeLa nuclear extracts, ASF/SF2, but not histone, phosphorylation was inhibited by poly(ADP-ribose); (ii) an in silico study based on gene expression profiling data revealed an increased incidence of alternative splicing within a subset of inflammatory response genes that are dysregulated in cells lacking a functional poly(ADP-ribose) polymerase-1. We propose that poly(ADP-ribose) targeting of topoisomerase I and ASF/SF2 functions may participate in the regulation of gene expression. | lld:pubmed |
| pubmed-article:18495665 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18495665 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18495665 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18495665 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:18495665 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:18495665 | pubmed:author | pubmed-author:GirstunAgnies... | lld:pubmed |
| pubmed-article:18495665 | pubmed:author | pubmed-author:MalangaMariaM | lld:pubmed |
| pubmed-article:18495665 | pubmed:author | pubmed-author:AlthausFelix... | lld:pubmed |
| pubmed-article:18495665 | pubmed:author | pubmed-author:CzubatyAlicja... | lld:pubmed |
| pubmed-article:18495665 | pubmed:author | pubmed-author:StaronKrzyszt... | lld:pubmed |
| pubmed-article:18495665 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18495665 | pubmed:day | 18 | lld:pubmed |
| pubmed-article:18495665 | pubmed:volume | 283 | lld:pubmed |
| pubmed-article:18495665 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18495665 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18495665 | pubmed:pagination | 19991-8 | lld:pubmed |
| pubmed-article:18495665 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
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| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:meshHeading | pubmed-meshheading:18495665... | lld:pubmed |
| pubmed-article:18495665 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18495665 | pubmed:articleTitle | Poly(ADP-ribose) binds to the splicing factor ASF/SF2 and regulates its phosphorylation by DNA topoisomerase I. | lld:pubmed |
| pubmed-article:18495665 | pubmed:affiliation | Department of Structural and Functional Biology, University Federico II, Via Cinthia, Monte S Angelo, Naples, Italy. malanga@unina.it | lld:pubmed |
| pubmed-article:18495665 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18495665 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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