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Content archived on 2024-06-18

Molecular analysis of single-strand break repair (SSBR) in human cells

Objective

DNA single-strand breaks (SSBs) can arise directly by the action of free radicalsor indirectly as intermediates of base excision repair or topoisomerase I activity. Moreover, replication can convert a SSB into a double-strand break (DSB), one of the most severe DNA lesions that can occur in living cells. Single-strand break repair (SSBR) is therefore crucial to ensure cell survival and the maintenance of genome stability. In addition, SSBR defects have been associated with some neurodegenerative diseases.The main goal of this project is to study the molecular mechanism/s of SSBR in human cells. Our primary focus will be to develop a novel system to induce a site-specific SSB in human cells. This will allow, for the first time, direct analysis of the assembly/disassembly of protein complexes at the SSB reaction by ChIP analyses, in addition to measuring the repair event itself. For example, we will examine the sequence of recruitment of the individual SSBR proteins, as well as identifying which proteins are required for assembly/disassembly/remodelling of protein complexes at chromosomal SSBs. This approach will also provide a system to examine possible SSBR defects in neurodegenerative diseases. We are particullary interested in defining the molecular role of APLF (aprataxin and PNK like factor), a SSBR protein recently identified in this laboratory.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2007-2-1-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE UNIVERSITY OF SUSSEX
EU contribution
€ 178 307,05
Address
SUSSEX HOUSE FALMER
BN1 9RH Brighton
United Kingdom

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Region
South East (England) Surrey, East and West Sussex Brighton and Hove
Activity type
Higher or Secondary Education Establishments
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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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