Damage-Induced Ubiquitylation of Human RNA Polymerase II by the Ubiquitin Ligase Nedd4, but Not Cockayne Syndrome Proteins or BRCA1
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Damage-Induced Ubiquitylation of Human RNA Polymerase II by the Ubiquitin Ligase Nedd4, but Not Cockayne Syndrome Proteins or BRCA1. / Anindya, Roy; Aygün, Ozan; Svejstrup, Jesper Q.
In: Molecular Cell, Vol. 28, No. 3, 09.11.2007, p. 386-397.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Damage-Induced Ubiquitylation of Human RNA Polymerase II by the Ubiquitin Ligase Nedd4, but Not Cockayne Syndrome Proteins or BRCA1
AU - Anindya, Roy
AU - Aygün, Ozan
AU - Svejstrup, Jesper Q.
N1 - Funding Information: This work was supported by grants from Cancer Research UK, the EU, and the Association for International Cancer Research (to J.Q.S.). We thank Drs. Stefan Roberts, Pete Snyder, Paul Biensiasz, Hideki Kobayashi, Tony Pawson, Annie Angers, Fiona McDonald, Allan Weissman, Takeshi Imamura, Stanley Cohen, and Azzedine Atfi for kind gifts of plasmids. We thank Stefan Sigurdsson for experimental help and Svejstrup lab members for helpful discussion. Peter Verrijzer and Tomas Lindahl are thanked for comments on the manuscript.
PY - 2007/11/9
Y1 - 2007/11/9
N2 - UV-induced RNA polymerase II (RNAPII) ubiquitylation and degradation are important DNA damage responses, conserved from yeast to man. However, the identity of the human enzymes that mediate these responses has been unclear. Previously, Cockayne syndrome proteins and BRCA1 were implicated in the process. Surprisingly, using a recently developed assay system, we found that these factors are not directly involved in RNAPII ubiquitylation. The defects in RNAPII ubiquitylation observed in CS cells are caused by an indirect mechanism: these cells shut down transcription in response to DNA damage, effectively depleting the substrate for ubiquitylation, namely elongating RNAPII. Instead, we identified Nedd4 as an E3 that associates with and ubiquitylates RNAPII in response to UV-induced DNA damage in human cells. Nedd4-dependent RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together, our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment and RNAPII ubiquitylation.
AB - UV-induced RNA polymerase II (RNAPII) ubiquitylation and degradation are important DNA damage responses, conserved from yeast to man. However, the identity of the human enzymes that mediate these responses has been unclear. Previously, Cockayne syndrome proteins and BRCA1 were implicated in the process. Surprisingly, using a recently developed assay system, we found that these factors are not directly involved in RNAPII ubiquitylation. The defects in RNAPII ubiquitylation observed in CS cells are caused by an indirect mechanism: these cells shut down transcription in response to DNA damage, effectively depleting the substrate for ubiquitylation, namely elongating RNAPII. Instead, we identified Nedd4 as an E3 that associates with and ubiquitylates RNAPII in response to UV-induced DNA damage in human cells. Nedd4-dependent RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together, our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment and RNAPII ubiquitylation.
KW - DNA
KW - PROTEINS
U2 - 10.1016/j.molcel.2007.10.008
DO - 10.1016/j.molcel.2007.10.008
M3 - Journal article
C2 - 17996703
AN - SCOPUS:35748950163
VL - 28
SP - 386
EP - 397
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 3
ER -
ID: 331007109