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Activation of a novel ubiquitin-independent proteasome pathway when RNA polymerase II encounters a protein roadblock.

ABSTRACT: Topoisomerase II? (Top2?)-DNA cleavage complexes are known to arrest elongating RNA polymerase II (RNAPII), triggering a proteasomal degradation of the RNAPII large subunit (RNAPII LS) and Top2? itself as a prelude to DNA repair. Here, we demonstrate that the degradation of Top2? 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 Top2? cleavage complex and coordinating its degradation by 20S proteasome when RNAPII is persistently stalled by the Top2? 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.

SUBMITTER: Ban Y

PROVIDER: S-EPMC3811683 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Activation of a novel ubiquitin-independent proteasome pathway when RNA polymerase II encounters a protein roadblock.

Ban Yi Y Ho Chia-Wen CW Lin Ren-Kuo RK Lyu Yi Lisa YL Liu Leroy F LF

Molecular and cellular biology 20130812 20

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 coordinat ...[more]

PMID: 23938298

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