TRANSINTEG

Transcription and the maintenance of genome integrity

 Coordinatore THE FRANCIS CRICK INSTITUTE LIMITED 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 1˙950˙000 €
 EC contributo 1˙950˙000 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2010-AdG_20100317
 Funding Scheme ERC-AG
 Anno di inizio 2011
 Periodo (anno-mese-giorno) 2011-05-01   -   2016-04-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    CANCER RESEARCH UK

 Organization address address: ST JOHN STREET 407 ANGEL BUILDING
city: LONDON
postcode: EC1V 4AD

contact info
Titolo: Ms.
Nome: Holly
Cognome: Elphinstone
Email: send email
Telefono: +44 207 269 3539
Fax: +44 207 269 3585

UK (LONDON) beneficiary 0.00
2    THE FRANCIS CRICK INSTITUTE LIMITED

 Organization address address: 215 Euston Road, Gibbs Building
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Dr.
Nome: Jesper Qualmann
Cognome: Svejstrup
Email: send email
Telefono: +44 1707 62 5960
Fax: +44 1707 62 5960

UK (LONDON) hostInstitution 1˙950˙000.00
3    THE FRANCIS CRICK INSTITUTE LIMITED

 Organization address address: 215 Euston Road, Gibbs Building
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Ms.
Nome: Heather Joanne
Cognome: Woods
Email: send email
Telefono: 442076000000

UK (LONDON) hostInstitution 1˙950˙000.00

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levels    transcription    coupled    gene    genes    repair    genome    dna    pathways    damage    crucial    maintaining    ubiquitylation    iquest    rnapii    integrity    mechanisms   

 Obiettivo del progetto (Objective)

'Maintaining genome integrity is crucial, especially in protein-encoding genes. DNA damage in genes can give rise to harmful mutations, but it can also directly obstruct the progress of transcribing RNA polymerase II (RNAPII), thereby blocking gene expression. Not surprisingly, repair pathways have evolved that specifically target lesions that stop RNAPII during its journey across a gene, so-called transcription-coupled repair pathways. As an alternative and ¿last resort¿, damage-stalled RNAPII can also be permanently removed by ubiquitylation/degradation, clearing the gene for repair by other means. Together, transcription-coupled repair and RNAPII ubiquitylation constitute an essential axis in the response to DNA damage. Conversely, while transcription is essential and therefore protected by a variety of mechanisms, it also itself comes at a cost for genome integrity. For example, high levels of transcription are correlated with breaks at fragile chromosome sites, mutagenesis and elevated levels of DNA recombination. Research into how the genome-destabilizing effects of transcription are minimized is still at an early stage, but insight into this research area is essential for our general appreciation of the regulatory mechanisms at play in the interface between transcription and other DNA-related processes, as well as for the understanding of processes underlying genome instability. This proposal describes how funding from the ERC will enable us to use a multi-disciplinary approach to shed new light on fundamental and disease-relevant processes, which are crucial for maintaining genome integrity during active transcription.'

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