Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double-strand break signaling and repair.

Molecular Cell
Sophie E PoloStephen P Jackson

Abstract

DNA double-strand break (DSB) signaling and repair are critical for cell viability, and rely on highly coordinated pathways whose molecular organization is still incompletely understood. Here, we show that heterogeneous nuclear ribonucleoprotein U-like (hnRNPUL) proteins 1 and 2 play key roles in cellular responses to DSBs. We identify human hnRNPUL1 and -2 as binding partners for the DSB sensor complex MRE11-RAD50-NBS1 (MRN) and demonstrate that hnRNPUL1 and -2 are recruited to DNA damage in an interdependent manner that requires MRN. Moreover, we show that hnRNPUL1 and -2 stimulate DNA-end resection and promote ATR-dependent signaling and DSB repair by homologous recombination, thereby contributing to cell survival upon exposure to DSB-inducing agents. Finally, we establish that hnRNPUL1 and -2 function downstream of MRN and CtBP-interacting protein (CtIP) to promote recruitment of the BLM helicase to DNA breaks. Collectively, these results provide insights into how mammalian cells respond to DSBs.

References

Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·E RaderschallT Haaf
Nov 27, 2001·Science·D CortezS J Elledge
Jun 7, 2003·Science·Lee Zou, Stephen J Elledge
Oct 9, 2003·The EMBO Journal·Tamar UzielYosef Shiloh
May 24, 2005·FEBS Letters·Paola M BarralRoger J A Grand
Aug 3, 2005·The Journal of Cell Biology·Jong-Soo KimKyoko Yokomori
Sep 16, 2005·The Journal of Biological Chemistry·Michela ClericiMaria Pia Longhese
Dec 6, 2005·Nature Cell Biology·Ali JazayeriStephen P Jackson
Apr 19, 2006·The Journal of Cell Biology·Simon Bekker-JensenJiri Lukas
Sep 21, 2007·Cell Cycle·Simone Difilippantonio, André Nussenzweig
Nov 15, 2007·The Journal of Biological Chemistry·Michael R Lieber
Dec 18, 2007·Molecular Cell·J Wade Harper, Stephen J Elledge
Jan 8, 2008·Nature Chemical Biology·Aude DupréJean Gautier
Feb 16, 2008·Annual Review of Biochemistry·Joseph San FilippoHannah Klein
Apr 16, 2008·The Journal of Cell Biology·Christoph SpycherManuel Stucki
May 16, 2008·Journal of Virology·Andrew N BlackfordAndrew S Turnell
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Aug 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Liming WuJunjie Chen
Oct 17, 2008·Genes & Development·Serge GravelStephen P Jackson
Jan 21, 2009·Cellular and Molecular Life Sciences : CMLS·B PardoA Aguilera
Apr 9, 2009·Biochemical and Biophysical Research Communications·Fredrik M Berglund, Paul R Clarke
Apr 21, 2009·Trends in Biochemical Sciences·Eleni P Mimitou, Lorraine S Symington
Jun 6, 2009·Cell·Kara A Bernstein, Rodney Rothstein
Jul 7, 2009·International Journal of Radiation Biology·Benjamin HaleyGayle E Woloschak
Sep 24, 2009·The Biochemical Journal·Andrea J Hartlerode, Ralph Scully
Oct 29, 2009·Chromosoma·Agnieszka RupnikMuriel Grenon
Jan 7, 2010·Nature Structural & Molecular Biology·Pablo Huertas
May 7, 2010·Trends in Cell Biology·Zhongsheng You, Julie M Bailis
Jul 22, 2010·The EMBO Journal·Maria Pia LongheseMichela Clerici
Aug 28, 2010·The Biochemical Journal·Siew Ping HanRoss Smith

❮ Previous
Next ❯

Citations

Feb 7, 2013·Nature Reviews. Molecular Cell Biology·Dipanjan ChowdhuryMarie Eve Brault
Jun 14, 2013·Nucleic Acids Research·Amelie CrosetMarie Dutreix
Mar 27, 2013·Molecular and Cellular Biology·Avvaru N SuhasiniRobert M Brosh
Feb 19, 2014·Trends in Biochemical Sciences·Martin DutertreStéphan Vagner
May 21, 2013·FEBS Letters·Vivek Sharma, Tom Misteli
Feb 20, 2016·Molecular Cell·Vihandha O Wickramasinghe, Ashok R Venkitaraman
Jul 18, 2014·Nucleic Acids Research·Sébastien BrittonPatrick Calsou
Dec 18, 2015·Nucleic Acids Research·Federico Teloni, Matthias Altmeyer
Oct 13, 2015·Molecular Cell·Paul WijnhovenStephen P Jackson
May 29, 2015·Scientific Reports·Gayathri GurunathanStéphane Richard
Aug 3, 2012·The Journal of General Virology·Andrew S Turnell, Roger J Grand
Aug 20, 2015·Nature Communications·Matthias AltmeyerJiri Lukas
May 10, 2015·DNA Repair·James M DaleyPatrick Sung
Apr 17, 2016·Nucleic Acids Research·David O OnyangoJeremy M Stark
Jun 23, 2015·Nature Communications·Yasushi MasudaShigetsugu Hatakeyama
Jun 12, 2013·Molecular Cell·Palaniraja ThandapaniStéphane Richard
Aug 21, 2012·Current Opinion in Cell Biology·Rebecca C BurgessPhilipp Oberdoerffer
Apr 30, 2016·Wiley Interdisciplinary Reviews. RNA·Jekaterina VohhodinaKienan I Savage
May 14, 2016·Acta Biochimica Et Biophysica Sinica·Sharad C Paudyal, Zhongsheng You
May 18, 2016·The Journal of Clinical Investigation·Qian WangLei Shi
Jun 1, 2016·Genomics, Proteomics & Bioinformatics·Huiting Wei, Xiaochun Yu
Aug 10, 2016·Nature Communications·Ana López-SaavedraPablo Huertas
Dec 3, 2014·Journal of Molecular Biology·Christian-Benedikt GerholdSusan M Gasser
Nov 9, 2016·Journal of Molecular Biology·Giuseppina D'Alessandro, Fabrizio d'Adda di Fagagna
Nov 9, 2016·Nature Communications·Zhaohui GuCharles G Mullighan
Feb 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jung-Kuei ChenHung-Wen Liu
Mar 2, 2016·International Journal of Molecular Sciences·Mihoko Kai

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.