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Defects in DNA strand break repair and links to inheritable disease

Cel

Our genetic material is continually subjected to damage, either from endogenous sources such as reactive oxygen species produced as by-products of oxidative metabolism, from the breakdown of replication forks during cell growth, or by agents in the environment such as ionising radiation or carcinogenic chemicals. To cope with DNA damage, cells employ elaborate and effective repair processes that specifically recognise a wide variety of lesions in DNA. These repair systems are essential for the maintenance of genome integrity. Unfortunately, some individuals are genetically predisposed to crippling diseases or cancers that are the direct result of mutations in genes involved in the DNA damage response. For several years our work has been at the forefront of basic biological research in the area of DNA repair, and in particular we have made significant contributions to the understanding of inheritable diseases such as breast cancer, Fanconi anemia, and the neurodegenerative disease Ataxia with Oculomotor Apraxia-1 (AOA-1). The focus of this ERC proposal is: (i) to define the phenotypic interplay between three inheritable cancer predisposition syndromes, Fanconi anemia, Bloom s syndrome and breast cancers caused by mutation of BRCA2, (ii) to determine the biological role of the newly discovered GEN1 Holliday junction resolvase in homologous recombination and repair, and (iii) to understand the actions of Aprataxin and Senataxin in relation to the inheritable neurodegenerative diseases AOA-1 and AOA-2, respectively. Our studies will provide an improved understanding of basic mechanisms of DNA repair and thereby underpin future therapeutic developments that will help individuals afflicted with these diseases.

Zaproszenie do składania wniosków

ERC-2009-AdG
Zobacz inne projekty w ramach tego zaproszenia

System finansowania

ERC-AG - ERC Advanced Grant

Instytucja przyjmująca

THE FRANCIS CRICK INSTITUTE LIMITED
Wkład UE
€ 2 449 091,40
Adres
1 MIDLAND ROAD
NW1 1AT London
Zjednoczone Królestwo

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Region
London Inner London — West Camden and City of London
Rodzaj działalności
Research Organisations
Kontakt administracyjny
Heather Joanne Woods (Ms.)
Kierownik naukowy
Stephen West (Dr.)
Linki
Koszt całkowity
Brak danych

Beneficjenci (2)