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TRANSDAM SIGNED

The transcription-related DNA damage response

Total Cost €

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EC-Contrib. €

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Partnership

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 TRANSDAM project word cloud

Explore the words cloud of the TRANSDAM project. It provides you a very rough idea of what is the project "TRANSDAM" about.

transcription    stalled    integration    performed    mrna    distinguish    instead    decision    thousands    places    basis    removed    genomic    describes    always    despite    hundreds    whereby    biochemical    expression    alternative    unprecedented    emphasis    techniques    cell    disciplinary    gene    cellular    dna    angles    screens    underlie    repair    rnapii    frequent    characterization    difficult    lesions    pursue    stalling    ed    poorly    eventual    uv    preferentially    genomics    nucleotide    omic    elongation    coupled    dramatically    mechanisms    irradiation    block    triggers    false    cease    explores    genes    normalization    biological    proteomics    scope    unexplored    splicing    grant    preliminary    effect    parallel    damage    sirna    bulky    proteomic    expressed    temporarily    hits    genome    identification    score    individual    transcript    complemented    excision    global    risk    impossible    damaged    screening    ing    enigmatic    positives    local    negative    decades    screen   

Project "TRANSDAM" data sheet

The following table provides information about the project.

Coordinator
THE FRANCIS CRICK INSTITUTE LIMITED 

Organization address
address: 1 MIDLAND ROAD
city: LONDON
postcode: NW1 1AT
website: www.crick.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.crick.ac.uk/research/labs/jesper-svejstrup
 Total cost 2˙499˙988 €
 EC max contribution 2˙499˙988 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 2˙499˙988.00

Map

 Project objective

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.

 Publications

year authors and title journal last update
List of publications.
2019 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
Methods 159-160 2019-10-31
2019 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
2019 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
2019 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
Cell 177/7 2019-10-29
2018 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
2017 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
2017 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
Cell 168/5 2019-06-14

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