Abstract
Topoisomerase IIβ (Top2β)-DNA cleavage complexes are known to arrest elongating RNA polymerase II (RNAPII), triggering a proteasomal degradation of the RNAPII large subunit (RNAPII LS) and Top2β itself as a prelude to DNA repair. Here, we demonstrate that the degradation of Top2β occurs through a novel ubiquitin-independent mechanism that requires only 19S AAA ATPases and 20S proteasome. Our results suggest that 19S AAA ATPases play a dual role in sensing the Top2β cleavage complex and coordinating its degradation by 20S proteasome when RNAPII is persistently stalled by the Top2β protein roadblock. Clarification of this transcription-associated proteasome pathway could shed light on a general role of 19S AAA ATPases in processing tight protein-DNA complexes during transcription elongation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphatases / genetics*
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Adenosine Triphosphatases / metabolism
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Animals
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DNA / genetics*
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DNA / metabolism
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DNA Repair*
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DNA Topoisomerases, Type II / genetics*
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DNA Topoisomerases, Type II / metabolism
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian
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Fibroblasts / cytology
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Fibroblasts / metabolism
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HeLa Cells
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Humans
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Mice
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Proteasome Endopeptidase Complex / genetics*
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Proteasome Endopeptidase Complex / metabolism
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Protein Binding
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RNA Polymerase II / genetics*
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RNA Polymerase II / metabolism
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Transcription Elongation, Genetic*
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Ubiquitin
Substances
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DNA-Binding Proteins
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Ubiquitin
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DNA
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RNA Polymerase II
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RNA polymerase II largest subunit
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Proteasome Endopeptidase Complex
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Adenosine Triphosphatases
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DNA Topoisomerases, Type II