Source:http://linkedlifedata.com/resource/pubmed/id/16949575
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
2006-9-22
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pubmed:abstractText |
Mutations in the RECQL4 helicase gene have been linked to Rothmund-Thomson syndrome (RTS), which is characterized by poikiloderma, growth deficiency, and a predisposition to cancer. Examination of RECQL4 subcellular localization in live cells demonstrated a nucleoplasmic pattern and, to a lesser degree, staining in nucleoli. Analysis of RECQL4-GFP deletion mutants revealed two nuclear localization regions in the N-terminal region of RECQL4 and a nucleolar localization signal at amino acids 376-386. RECQL4 localization did not change after treatment with the DNA-damaging agents bleomycin, etoposide, UV irradiation and gamma irradiation, in contrast to the Bloom and Werner syndrome helicases that relocate to distinct nuclear foci after damage. However, in a significant number of cells exposed to hydrogen peroxide or streptonigrin, RECQL4 accumulated in nucleoli. Using a T7 phage display screen, we determined that RECQL4 interacts with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme that promotes genomic integrity through its involvement in DNA repair and signaling pathways. The RECQL4 nucleolar localization was inhibited by pretreatment with a PARP-1 inhibitor. The C-terminal portion of RECQL4 was found to be an in vitro substrate for PARP-1. These results demonstrate changes in the intracellular localization of RECQL4 in response to oxidative stress and identify an interaction between RECQL4 and PARP-1.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PARP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/RECQL4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RecQ Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
312
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3443-57
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16949575-Adenosine Triphosphatases,
pubmed-meshheading:16949575-Cell Line,
pubmed-meshheading:16949575-Cell Nucleolus,
pubmed-meshheading:16949575-Cell Nucleus,
pubmed-meshheading:16949575-DNA Helicases,
pubmed-meshheading:16949575-Green Fluorescent Proteins,
pubmed-meshheading:16949575-HeLa Cells,
pubmed-meshheading:16949575-Humans,
pubmed-meshheading:16949575-Oxidative Stress,
pubmed-meshheading:16949575-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:16949575-RecQ Helicases
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pubmed:year |
2006
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pubmed:articleTitle |
The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress.
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pubmed:affiliation |
Department of Pathology, University of Chicago, MC1089, Chicago, IL 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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