Abstract
The ligase IV/XRCC4 complex plays a central role in DNA double-strand break repair by non-homologous end joining (NHEJ). During adenovirus infection, NHEJ is inhibited by viral proteins E4 34k and E1B 55k, which redirect the Cul5/Rbx1/Elongin BC ubiquitin E3 ligase to polyubiquitinate and promote degradation of ligase IV. In cells infected with E1B 55k-deficient adenovirus, ligase IV could not be found in XRCC4-containing complexes and was observed in a novel ligase IV/E4 34k/Cul5/Elongin BC complex. These observations suggest that dissociation of the ligase IV/XRCC4 complex occurs at an early stage in E4 34k-mediated degradation of ligase IV and indicate a role for E4 34k in dissociation of the ligase IV/XRCCC4 complex. Expression of E4 34k alone was not sufficient to dissociate the ligase IV/XRCC4 complex, which indicates a requirement for an additional, as yet unidentified, factor in E1B 55k-independent dissociation of the ligase IV/XRCC4 complex.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenovirus E1B Proteins / chemistry
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Adenovirus E1B Proteins / genetics
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Adenovirus E1B Proteins / metabolism*
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Adenovirus E4 Proteins / chemistry
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Adenovirus E4 Proteins / genetics
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Adenovirus E4 Proteins / metabolism*
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Adenovirus Infections, Human / metabolism
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Adenovirus Infections, Human / virology
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Adenoviruses, Human / genetics
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Adenoviruses, Human / pathogenicity*
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Adenoviruses, Human / physiology*
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Cullin Proteins / chemistry
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Cullin Proteins / metabolism
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DNA Breaks, Double-Stranded
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DNA Ligase ATP
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DNA Ligases / chemistry
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DNA Ligases / metabolism*
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DNA Repair
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Elongin
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Gene Deletion
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Genes, Viral
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HeLa Cells
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Humans
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Models, Biological
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Multiprotein Complexes
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Transcription Factors / chemistry
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Transcription Factors / metabolism
Substances
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Adenovirus E1B Proteins
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Adenovirus E4 Proteins
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CUL5 protein, human
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Cullin Proteins
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DNA-Binding Proteins
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Elongin
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LIG4 protein, human
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Multiprotein Complexes
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Transcription Factors
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XRCC4 protein, human
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DNA Ligases
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DNA Ligase ATP