Activation of a novel ubiquitin-independent proteasome pathway when RNA polymerase II encounters a protein roadblock.
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.
Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA.
Yi
Y
Ban
Chia-Wen
CW
Ho
Ren-Kuo
RK
Lin
Yi Lisa
YL
Lyu
Leroy F
LF
Liu
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D025801:Ubiquitin
D004268:DNA-Binding Proteins; D025801:Ubiquitin; D004247:DNA; D012319:RNA Polymerase II; C410949:RNA polymerase II largest subunit; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II