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  Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair

Seoane, M., Buhs, S., Iglesias, P., Strauss, J., Puller, A.-C., Müller, J., et al. (2019). Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair. Oncogene, 38(19), 3616-3635. doi:10.1038/s41388-018-0661-x.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-A548-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-A54E-C
Genre: Journal Article

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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
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https://dx.doi.org/10.1038/s41388-018-0661-x (Publisher version)
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 Creators:
Seoane, M.1, 2, Author
Buhs, S.1, 2, Author
Iglesias, P.1, 2, Author
Strauss, J.1, 2, Author
Puller, A.-C.1, 2, Author
Müller, J.1, 2, Author
Gerull, H.1, 2, Author
Feldhaus, S.3, Author
Alawi, M.4, 5, Author
Brandner, J. M.6, Author
Eggert, D.5, 7, Author              
Du, J.8, Author
Thomale, J.9, Author
Wild, P. J.10, Author
Zimmermann, M.11, Author
Sternsdorf, T.1, 2, Author
Schumacher, U.3, Author
Nollau, P.1, 2, Author
Fisher, D. E.12, Author
Horstmann, M. A.1, 2, Author
Affiliations:
1Research Institute Children’s Cancer Center Hamburg, ou_persistent22              
2Department of Pediatric Hematology and Oncology, UniversityMedical Center Hamburg, ou_persistent22              
3Institute of Anatomy and Experimental Morphology, University Medical Center Hamburg, ou_persistent22              
4Bioinformatics Service Facility, University Medical Center Hamburg, ou_persistent22              
5Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, ou_persistent22              
6Department of Dermatology, University Medical Center Hamburg, ou_persistent22              
7Miller Group, Atomically Resolved Dynamics Department, Max Planck Institute for the Structure and Dynamics of Matter, Max Planck Society, ou_1938288              
8Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, ou_persistent22              
9Institute of Cell Biology, University Duisburg-Essen, ou_persistent22              
10Institute of Surgical Pathology, University Hospital Zürich, ou_persistent22              
11Department of Pediatric Hematology and Oncology, Medical School Hannover, ou_persistent22              
12Department of Dermatology, Cutaneous Biology Research Center,Massachusetts General Hospital, Harvard Medical School, Boston, ou_persistent22              

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 Abstract: The melanocytic lineage, which is prominently exposed to ultraviolet radiation (UVR) and radiation-independent oxidative damage, requires specific DNA-damage response mechanisms to maintain genomic and transcriptional homeostasis. The coordinate lineage-specific regulation of intricately intertwined DNA repair and transcription is incompletely understood. Here we demonstrate that the Microphthalmia-associated transcription factor (MITF) directly controls general transcription and UVR-induced nucleotide excision repair by transactivation of GTF2H1 as a core element of TFIIH. Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. Moreover, MITF controls c-MYC implicated in general transcription by transactivation of far upstream binding protein 2 (FUBP2/KSHRP), which induces c-MYC pulse regulation through TFIIH, and experimental depletion of MITF results in consecutive loss of CDK7 in the TFIIH-CAK subcomplex. Targeted for proteasomal degradation, CDK7 is dependent on transactivation by MITF or c-MYC to maintain a steady state. The dependence of TFIIH-CAK on sequence-specific MITF and c-MYC constitutes a previously unrecognized mechanism feeding into super-enhancer-driven or other oncogenic transcriptional circuitries, which supports the concept of a transcription-directed therapeutic intervention in melanoma.

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Language(s): eng - English
 Dates: 2018-09-252018-12-052019-01-162019-05-09
 Publication Status: Published in print
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41388-018-0661-x
 Degree: -

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Project name : Deutsche Forschungsgemeinschaft (DFG) grants to M.A.H. (Ho2176/3-1/2), Fördergemeinschaft Kinderkrebs-Zentrum Hamburg and the Rüdiger Colditz Stiftung. We gratefully acknowledge help from members of the Grundhoff lab for technical support and members of the microscopy and imaging group, both at the Heinrich- Pette-Institute, Hamburg. We also thank Ewa Wladykowski, Christine Knies, and Tobias Gosau for technical assistance.
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Title: Oncogene
Source Genre: Journal
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Publ. Info: Basingstoke, Hampshire, UK : Nature Publishing Group
Pages: 20 Volume / Issue: 38 (19) Sequence Number: - Start / End Page: 3616 - 3635 Identifier: ISSN: 0950-9232
CoNE: https://pure.mpg.de/cone/journals/resource/954925574955