دورية أكاديمية
MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response
| العنوان: | MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response |
|---|---|
| المؤلفون: | Pothof, Joris, Verkaik, Nicole, van Ijcken, Wilfred, Wiemer, Erik, Ta, Van, van der Horst, Bert, Jaspers, Koos, van Gent, Dik, Hoeijmakers, Jan, Persengiev, SP |
| المصدر: | Pothof , J , Verkaik , N , van Ijcken , W , Wiemer , E , Ta , V , van der Horst , B , Jaspers , K , van Gent , D , Hoeijmakers , J & Persengiev , SP 2009 , ' MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response ' , EMBO Journal , vol. 28 , no. 14 , pp. 2090-2099 . https://doi.org/10.1038/emboj.2009.156Test |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMGC011203, name=EMC MGC-01-12-03, /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMGC021302, name=EMC MGC-02-13-02, /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM038608, name=EMC MM-03-86-08, /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM044202, name=EMC MM-04-42-02 |
| الوصف: | DNA damage provokes DNA repair, cell-cycle regulation and apoptosis. This DNA-damage response encompasses gene-expression regulation at the transcriptional and post-translational levels. We show that cellular responses to UV-induced DNA damage are also regulated at the post-transcriptional level by microRNAs. Survival and checkpoint response after UV damage was severely reduced on microRNA-mediated gene-silencing inhibition by knocking down essential components of the microRNA-processing pathway (Dicer and Ago2). UV damage triggered a cell-cycle-dependent relocalization of Ago2 into stress granules and various microRNA-expression changes. Ago2 relocalization required CDK activity, but was independent of ATM/ATR checkpoint signalling, whereas UV-responsive microRNA expression was only partially ATM/ATR independent. Both microRNA-expression changes and stress-granule formation were most pronounced within the first hours after genotoxic stress, suggesting that microRNA-mediated gene regulation operates earlier than most transcriptional responses. The functionality of the microRNA response is illustrated by the UV-inducible miR-16 that downregulates checkpoint-gene CDC25a and regulates cell proliferation. We conclude that microRNA-mediated gene regulation adds a new dimension to the DNA-damage response. The EMBO Journal (2009) 28, 2090-2099. doi:10.1038/emboj.2009.156; Published online 18 June 2009 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://pure.eur.nl/en/publications/1759e8e8-81de-4910-9742-0078c62595b4Test |
| DOI: | 10.1038/emboj.2009.156 |
| الإتاحة: | https://doi.org/10.1038/emboj.2009.156Test https://pure.eur.nl/en/publications/1759e8e8-81de-4910-9742-0078c62595b4Test http://hdl.handle.net/1765/24553Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.29F47091 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/emboj.2009.156 |
|---|