Inhibition of UVSSA ubiquitination suppresses transcription‐coupled nucleotide excision repair deficiency caused by dissociation from USP7

Inhibition of UVSSA ubiquitination suppresses transcription‐coupled nucleotide excision repair... Transcription‐coupled nucleotide excision repair (TC‐NER) is a subpathway of nucleotide excision repair that efficiently removes transcription‐blocking DNA damage from the transcribed strands of active genes. UVSSA is a causative gene for UV‐sensitive syndrome (UVSS), which is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in TC‐NER. UV‐stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with ubiquitin‐specific peptidase 7 (USP7) and is stabilized by interaction with USP7. The central region of UVSSA, which contains the tumor necrosis factor receptor‐associated factor (TRAF)‐binding motif, is required for the interaction with the N‐terminal TRAF domain of USP7. Here, we showed that UVSSA is mono‐ubiquitinated in vitro and identified a lysine residue (Lys414) in UVSSA as the target of ubiquitination. The deubiquitination activity of USP7 was inhibited by the ubiquitin‐conjugating enzyme UbcH6. Lys414 was also modified by poly‐ubiquitin chains in vivo. UVSSA deficient in the interaction with USP7 is ubiquitinated and degraded by the proteasome, and the degradation leads to deficiency in TC‐NER. The substitution of Lys414 by Arg of UVSSA inhibited its degradation and thereby suppressed the deficiency in TC‐NER. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Febs Journal Wiley

Inhibition of UVSSA ubiquitination suppresses transcription‐coupled nucleotide excision repair deficiency caused by dissociation from USP7

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Publisher
Wiley
Copyright
Copyright © 2018 Federation of European Biochemical Societies
ISSN
1742-464X
eISSN
1742-4658
D.O.I.
10.1111/febs.14382
Publisher site
See Article on Publisher Site

Abstract

Transcription‐coupled nucleotide excision repair (TC‐NER) is a subpathway of nucleotide excision repair that efficiently removes transcription‐blocking DNA damage from the transcribed strands of active genes. UVSSA is a causative gene for UV‐sensitive syndrome (UVSS), which is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in TC‐NER. UV‐stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with ubiquitin‐specific peptidase 7 (USP7) and is stabilized by interaction with USP7. The central region of UVSSA, which contains the tumor necrosis factor receptor‐associated factor (TRAF)‐binding motif, is required for the interaction with the N‐terminal TRAF domain of USP7. Here, we showed that UVSSA is mono‐ubiquitinated in vitro and identified a lysine residue (Lys414) in UVSSA as the target of ubiquitination. The deubiquitination activity of USP7 was inhibited by the ubiquitin‐conjugating enzyme UbcH6. Lys414 was also modified by poly‐ubiquitin chains in vivo. UVSSA deficient in the interaction with USP7 is ubiquitinated and degraded by the proteasome, and the degradation leads to deficiency in TC‐NER. The substitution of Lys414 by Arg of UVSSA inhibited its degradation and thereby suppressed the deficiency in TC‐NER.

Journal

Febs JournalWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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