Valosin-containing Protein (VCP)/p97 Segregase Mediates Proteolytic Processing of Cockayne Syndrome Group B (CSB) in Damaged Chromatin.

The Journal of Biological Chemistry
Jinshan HeAltaf A Wani

Abstract

Cockayne syndrome group A and B (CSB) proteins act in transcription-coupled repair, a subpathway of nucleotide excision repair. Here we demonstrate that valosin-containing protein (VCP)/p97 segregase functions in ultraviolet radiation (UVR)-induced ubiquitin-mediated CSB degradation. We show that VCP/p97 inhibition and siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 impair CSB degradation. VCP/p97 inhibition also results in the accumulation of CSB in chromatin. Moreover, VCP/p97 interacts with both native and ubiquitin-conjugated forms of CSB. The localized cellular UVR exposures lead to VCP/p97 accumulation at DNA damage spots, forming distinct UVR-induced foci. However, manifestation of VCP/p97 foci is independent of CSB and UBXD7. Furthermore, VCP/p97 and UBXD7 associate with the Cockayne syndrome group A-DDB1-Cul4A complex, an E3 ligase responsible for CSB ubiquitination. Compromising proteasome and VCP/p97 function allows accumulation of both native and ubiquitinated CSB and results in an increase of UBXD7, proteasomal RPN2, and Sug1 in the chromatin compartment. Surprisingly, both biochemical inhibition and genetic defect of VCP/p97 enhance the recovery of RNA synthesis following UVR, whereas both VCP/...Continue Reading

References

Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·D B BregmanS L Warren
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·C P Selby, A Sancar
Apr 10, 1999·Genes & Development·W L de LaatJ H Hoeijmakers
Aug 21, 2001·Molecular Cell·M VolkerL H Mullenders
Dec 12, 2001·Molecular Biology of the Cell·N W BaysR Y Hampton
Jan 29, 2002·Nature Cell Biology·Ernst JaroschThomas Sommer
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Jesper Q Svejstrup
Jan 1, 2003·Journal of Cell Science·Jesper Q Svejstrup
Aug 29, 2003·The Journal of Biological Chemistry·Maureen E FitchJames M Ford
Apr 3, 2004·Nature·Jordan M CumminsBert Vogelstein
Jul 1, 2004·The Journal of Cell Biology·Vincent van den BoomWim Vermeulen
Jul 21, 2005·Nucleic Acids Research·Qi-En WangAltaf A Wani
Mar 11, 2006·The Journal of Biological Chemistry·Mohamed A El-MahdyAltaf A Wani
Jun 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·John C NewmanAlan M Weiner
Aug 22, 2008·The Journal of Biological Chemistry·Jeong-Sun JuConrad C Weihl
Sep 9, 2008·Cell·Gabriela AlexandruRaymond J Deshaies
Jan 8, 2011·Molecular Cell·Rati VermaRaymond J Deshaies
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Tsui-Fen ChouRaymond J Deshaies
Jul 12, 2011·Trends in Biochemical Sciences·Alexandra StolzDieter H Wolf
Oct 25, 2011·Nature Cell Biology·Mayura MeerangKristijan Ramadan
Nov 29, 2011·Nature Structural & Molecular Biology·Klara AcsNico P Dantuma
Feb 3, 2012·Nature Cell Biology·Hemmo MeyerSebastian Bremer
Apr 3, 2012·Nature Genetics·Petra SchwertmanJurgen A Marteijn
Apr 3, 2012·Nature Structural & Molecular Biology·Willem den BestenRaymond J Deshaies
Jun 15, 2012·BMC Biology·Hemmo Meyer
Apr 29, 2014·Nature Communications·Marjo-Riitta PuumalainenHanspeter Naegeli
Sep 25, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yuming WangJesper Q Svejstrup

❮ Previous
Next ❯

Citations

May 21, 2016·Frontiers in Genetics·André FranzThorsten Hoppe
Oct 19, 2016·International Journal of Molecular Sciences·Khosrow Rezvani
Oct 4, 2016·Photochemistry and Photobiology·Qianzheng Zhu, Altaf A Wani
Dec 9, 2016·Cell Cycle·Shalaka Chitale, Holger Richly
Aug 19, 2017·The Biochemical Journal·Lasse Stach, Paul S Freemont
Mar 18, 2021·Mechanisms of Ageing and Development·Elena Paccosi, Luca Proietti-De-Santis
Jun 11, 2021·Nature Cell Biology·Marit E GeijerJurgen A Marteijn

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.