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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
53
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pubmed:dateCreated |
2004-12-23
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pubmed:abstractText |
The efficient repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity. In mammalian cells, the nonhomologous end-joining process that represents the predominant repair pathway relies on the DNA-dependent protein kinase (DNA-PK) and the XRCC4-DNA ligase IV complex. Nonetheless, several in vitro and in vivo results indicate that mammalian cells use more than a single end-joining mechanism. While searching for a DNA-PK-independent end-joining activity, we found that the pretreatment of DNA-PK-proficient and -deficient rodent cells with an inhibitor of the poly(ADP-ribose) polymerase-1 enzyme (PARP-1) led to increased cytotoxicity of the highly efficient DNA double-strand breaking compound calicheamicin gamma1. In addition, the repair kinetics of the DSBs induced by calicheamicin gamma1 was delayed both in PARP-1-proficient cells pretreated with the PARP-1 inhibitor and in PARP-1-deficient cells. In order to get new insights into the mechanism of an alternative route for DSBs repair, we have established a new synapsis and end-joining two-step assay in vitro, operating on DSBs with either nuclear protein extracts or recombinant proteins. We found an end-joining activity independent of the DNA-PK/XRCC4-ligase IV complex but that actually required a novel synapsis activity of PARP-1 and the ligation activity of the XRCC1-DNA ligase III complex, proteins otherwise involved in the base excision repair pathway. Taken together, these results strongly suggest that a PARP-1-dependent DSBs end-joining activity may exist in mammalian cells. We propose that this mechanism could act as an alternative route of DSBs repair that complements the DNA-PK/XRCC4/ligase IV-dependent nonhomologous end-joining.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aminoglycosides,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA ligase (ATP),
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enediynes,
http://linkedlifedata.com/resource/pubmed/chemical/H2AX protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/X-ray repair cross complementing...,
http://linkedlifedata.com/resource/pubmed/chemical/calicheamicin gamma(1)I
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
55117-26
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15498778-Aminoglycosides,
pubmed-meshheading:15498778-Animals,
pubmed-meshheading:15498778-Antibiotics, Antineoplastic,
pubmed-meshheading:15498778-Cell Nucleus,
pubmed-meshheading:15498778-Cricetinae,
pubmed-meshheading:15498778-DNA,
pubmed-meshheading:15498778-DNA, Complementary,
pubmed-meshheading:15498778-DNA Damage,
pubmed-meshheading:15498778-DNA Ligases,
pubmed-meshheading:15498778-DNA Repair,
pubmed-meshheading:15498778-DNA-Binding Proteins,
pubmed-meshheading:15498778-Dose-Response Relationship, Drug,
pubmed-meshheading:15498778-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15498778-Enediynes,
pubmed-meshheading:15498778-Fibroblasts,
pubmed-meshheading:15498778-HeLa Cells,
pubmed-meshheading:15498778-Histones,
pubmed-meshheading:15498778-Humans,
pubmed-meshheading:15498778-Immunoblotting,
pubmed-meshheading:15498778-Kinetics,
pubmed-meshheading:15498778-Mice,
pubmed-meshheading:15498778-Models, Biological,
pubmed-meshheading:15498778-Models, Genetic,
pubmed-meshheading:15498778-Mutagens,
pubmed-meshheading:15498778-Mutation,
pubmed-meshheading:15498778-Oligonucleotides,
pubmed-meshheading:15498778-Phosphorylation,
pubmed-meshheading:15498778-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:15498778-Recombinant Proteins,
pubmed-meshheading:15498778-Time Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining.
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pubmed:affiliation |
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, F-31077 Toulouse Cedex, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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