Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair

Cell
Yuka NakazawaTomoo Ogi

Abstract

Transcription-coupled nucleotide excision repair (TC-NER) is initiated by the stalling of elongating RNA polymerase II (RNAPIIo) at DNA lesions. The ubiquitination of RNAPIIo in response to DNA damage is an evolutionarily conserved event, but its function in mammals is unknown. Here, we identified a single DNA damage-induced ubiquitination site in RNAPII at RPB1-K1268, which regulates transcription recovery and DNA damage resistance. Mechanistically, RPB1-K1268 ubiquitination stimulates the association of the core-TFIIH complex with stalled RNAPIIo through a transfer mechanism that also involves UVSSA-K414 ubiquitination. We developed a strand-specific ChIP-seq method, which revealed RPB1-K1268 ubiquitination is important for repair and the resolution of transcriptional bottlenecks at DNA lesions. Finally, RPB1-K1268R knockin mice displayed a short life-span, premature aging, and neurodegeneration. Our results reveal RNAPII ubiquitination provides a two-tier protection mechanism by activating TC-NER and, in parallel, the processing of DNA damage-stalled RNAPIIo, which together prevent prolonged transcription arrest and protect against neurodegeneration.

References

Jan 1, 1991·Methods in Enzymology·S MorenoP Nurse
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·D B BregmanS L Warren
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Jul 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·L LommelK S Sweder
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
May 12, 2005·The Journal of Biological Chemistry·Lea M StaritaNatsuko Chiba
May 21, 2005·Genes & Development·Frida E KleimanJames L Manley
Jan 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·R R LaposaJ E Cleaver
Feb 10, 2007·Science·Florian BruecknerPatrick Cramer
Nov 22, 2008·Nature Reviews. Molecular Cell Biology·Philip C Hanawalt, Graciela Spivak
Apr 11, 2009·Nature·Teresa A SoucySteven P Langston
May 12, 2009·Mutation Research·Kalindi ParmarLaura J Niedernhofer
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
May 4, 2010·Cell·Peter B RahlRichard A Young
Apr 7, 2011·Mechanisms of Ageing and Development·Thierry Nouspikel
Jul 8, 2011·Nature·Frédéric LangevinKetan J Patel
Apr 3, 2012·Nature Genetics·Petra SchwertmanJurgen A Marteijn
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Jul 10, 2012·Magnetic Resonance Imaging·Andriy FedorovRon Kikinis
Feb 23, 2013·Mechanisms of Ageing and Development·Vincent Laugel
Aug 27, 2013·Methods : a Companion to Methods in Enzymology·Michelle T PaulsenMats Ljungman
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel

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Citations

Sep 20, 2020·International Journal of Cancer. Journal International Du Cancer·Xihan GuoXu Wang
Sep 17, 2020·International Journal of Molecular Sciences·Philippe Johann To Berens, Jean Molinier
May 2, 2020·Nature Communications·Yana van der WeegenMartijn S Luijsterburg
Aug 9, 2020·Nature Reviews. Genetics·Dali ZongAndré Nussenzweig
Aug 18, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Yanfei LiuRui Gao
Nov 20, 2020·Nucleic Acids Research·Masahiko OkudaYoshifumi Nishimura
Dec 15, 2020·The Journal of Experimental Medicine·Katja ApeltMartijn S Luijsterburg
Jan 7, 2021·The Journal of Cell Biology·Mai SatoJean Gautier
Dec 4, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Juntaek OhDong Wang
Nov 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Elena PaccosiLuca Proietti-De-Santis
Nov 20, 2020·Nature Reviews. Molecular Cell Biology·Melvin Noe GonzalezJesper Q Svejstrup
Nov 24, 2020·ELife·Fanny EybouletFrançois Robert
Feb 17, 2021·Nucleic Acids Research·Vinod TiwariVilhelm A Bohr
Dec 6, 2020·Genes·Wojciech StrzałkaAgnieszka Katarzyna Banaś
Feb 28, 2021·Nature Communications·Diana van den HeuvelMartijn S Luijsterburg
Mar 10, 2021·Trends in Cell Biology·Diana van den HeuvelMartijn S Luijsterburg
Mar 30, 2021·EMBO Reports·Kevin G Mark, Michael Rape
Apr 30, 2021·Nature·Björn SchumacherJan H J Hoeijmakers
Jun 11, 2021·Nature Cell Biology·Christopher J Carnie, Stephen P Jackson
Jun 11, 2021·Nature Cell Biology·Marit E GeijerJurgen A Marteijn
Jun 11, 2021·Nature Cell Biology·Yana van der WeegenMartijn S Luijsterburg
Jul 3, 2021·International Journal of Molecular Sciences·Heling WangEvandro F Fang
Jul 3, 2021·International Journal of Molecular Sciences·Yuliya KrasikovaOlga Lavrik
Jul 3, 2021·International Journal of Molecular Sciences·Laura Curti, Stefano Campaner
Jul 17, 2021·Nucleic Acids Research·Masahiko OkudaYoshifumi Nishimura
Aug 21, 2021·DNA Repair·Liam Gaul, Jesper Q Svejstrup
Aug 23, 2021·DNA Repair·Oluwasegun T Akinniyi, Joseph C Reese
Sep 17, 2021·Nature·Goran KokicPatrick Cramer
Sep 23, 2021·Nucleic Acids Research·Jana Wiedermannová, Libor Krásný
Sep 25, 2021·Journal of the American Chemical Society·Ying TanYinsheng Wang

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