Explore the words cloud of the TRANSDAM project. It provides you a very rough idea of what is the project "TRANSDAM" about.
The following table provides information about the project.
THE FRANCIS CRICK INSTITUTE LIMITED
|Coordinator Country||United Kingdom [UK]|
|Total cost||2˙499˙988 €|
|EC max contribution||2˙499˙988 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2016-09-01 to 2021-08-31|
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|1||THE FRANCIS CRICK INSTITUTE LIMITED||UK (LONDON)||coordinator||2˙499˙988.00|
The cellular response to bulky DNA lesions, such as those induced by UV-irradiation, remains enigmatic despite decades of study. The effect of such damage on transcription is complex. At the local level, lesions cause stalling of RNAPII, resulting in a block to transcript elongation. Stalled RNAPII triggers transcription-coupled nucleotide excision repair, a process whereby lesions in genes are preferentially removed. Importantly, however, UV-irradiation also affects transcription genome-wide, so that even genes that are not damaged temporarily cease to be expressed. Alternative mRNA splicing also changes dramatically. The mechanisms and factors that underlie the global, damage-induced changes in gene expression, and its eventual normalization, are poorly understood. In order to facilitate identification of new factors and mechanisms involved in this response, we performed several distinct proteomic screens and an siRNA screen in parallel. This was complemented by characterization of transcription and mRNA splicing after DNA damage by genome-wide techniques. Any screening for new factors is high-risk, and the decision on which ‘hits’ to pursue is always difficult. Indeed, in any individual proteomic or genomic screen it is often impossible to distinguish ‘real’ hits from hundreds, if not thousands, of false-positives, and false-negative results are very frequent as well. Our multi-omic approach explores the same process from various angles and places less emphasis on hits from an individual screen and instead focuses on factors that score in several screens. This integration of screen results has resulted in the identification of several new factors and unexplored mechanisms. With a basis in exciting preliminary findings, this grant proposal thus describes a multi-disciplinary approach, including biochemical and cell biological approaches as well as proteomics and genomics, to characterize the transcription-related DNA damage response with an unprecedented scope.
|year||authors and title||journal||last update|
Ana Tufegdzic Vidakovic, Michelle Harreman, A. Barbara Dirac-Svejstrup, Stefan Boeing, Anindya Roy, Vesela Encheva, Michelle Neumann, Marcus Wilson, Ambrosius P. Snijders, Jesper Q. Svejstrup
Analysis of RNA polymerase II ubiquitylation and proteasomal degradation
published pages: 146-156, ISSN: 1046-2023, DOI: 10.1016/j.ymeth.2019.02.005
Diana Zatreanu, Zhong Han, Richard Mitter, Emanuela Tumini, Hannah Williams, Lea Gregersen, A. Barbara Dirac-Svejstrup, Stefania Roma, Aengus Stewart, Andres Aguilera, Jesper Q. Svejstrup
Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability
published pages: 57-69.e9, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.07.037
|Molecular Cell 76/1||2019-10-31|
Aylin Cakiroglu, Cedric R. Clapier, Andreas H. Ehrensberger, Elodie Darbo, Bradley R. Cairns, Nicholas M. Luscombe, Jesper Q. Svejstrup
Genome-wide reconstitution of chromatin transactions reveals that RSC preferentially disrupts H2AZ-containing nucleosomes
published pages: 988-998, ISSN: 1088-9051, DOI: 10.1101/gr.243139.118
|Genome Research 29/6||2019-10-29|
Lea H. Gregersen, Richard Mitter, Alejandro P. Ugalde, Takayuki Nojima, Nicholas J. Proudfoot, Reuven Agami, Aengus Stewart, Jesper Q. Svejstrup
SCAF4 and SCAF8, mRNA Anti-Terminator Proteins
published pages: 1797-1813.e18, ISSN: 0092-8674, DOI: 10.1016/j.cell.2019.04.038
Lea H. Gregersen, Jesper Q. Svejstrup
The Cellular Response to Transcription-Blocking DNA Damage
published pages: 327-341, ISSN: 0968-0004, DOI: 10.1016/j.tibs.2018.02.010
|Trends in Biochemical Sciences 43/5||2019-06-06|
Juston C. Weems, Brian D. Slaughter, Jay R. Unruh, Stefan Boeing, Shawn M. Hall, Merry B. McLaird, Takashi Yasukawa, Teijiro Aso, Jesper Q. Svejstrup, Joan W. Conaway, Ronald C. Conaway
Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage
published pages: 6431-6437, ISSN: 0021-9258, DOI: 10.1074/jbc.C117.777946
|Journal of Biological Chemistry 292/16||2019-06-14|
Laura Williamson, Marco Saponaro, Stefan Boeing, Philip East, Richard Mitter, Theodoros Kantidakis, Gavin P. Kelly, Anna Lobley, Jane Walker, Bradley Spencer-Dene, Michael Howell, Aengus Stewart, Jesper Q. Svejstrup
UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene
published pages: 843-855.e13, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.01.019
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