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Content archived on 2024-05-30

Transcription and the maintenance of genome integrity

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.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2010-AdG_20100317
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-AG - ERC Advanced Grant

Host institution

THE FRANCIS CRICK INSTITUTE LIMITED
EU contribution
€ 1 950 000,00
Address
1 MIDLAND ROAD
NW1 1AT London
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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Beneficiaries (2)

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