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Checkpoints, DNA damage response and cancer

Objective

The DNA Damage Response (DDR) protects the genome from cytotoxic and mutagenic effects of chemicals and radiation in the environment. Genetic defects in DDR lead to genome instability and predispose individuals to diseases like cancer. DDR is a rapid, dynamic and integrated response to genome insult which co- ordinates cell cycle progression, DNA replication and DNA repair. Our understanding of DDR has been based largely on the use of specific approaches in specific model organisms: e.g. genetics in yeast, biochemistry in frogs, cytology in mammalian cells, etc. The participating teams are experts with these model organisms who are committed to expanding their repertoire of technical and conceptual approaches to studying DDR. Our objectives are:
- To characterize mechanisms of genome surveillance in response to DNA damage and DNA replication stress by studying several key components (PI(3)- related kinases and associated subunits, Sgs1 helicasef PCNA and RF-C-related DDR components).
- To examine the role of novel Components of the DNA damage signal transduction pathway.
- To characterize the downstream effects of DDR on DNA replication, chromatin structure and ubiquit in mediated proteolysis. In each case, a multidisciplinary approach will involve the study of processes and proteins in different organisms using different technical strategies. This unique European collaboration will lead to new advances and contribute to an integrated view of DDR in eukaryotic cells.

Funding Scheme

NET - Research network contracts

Coordinator

CANCER RESEARCH UK
Address
Clare Hall Laboratories, Blanche Lane
EN6 3LD Potters Bar
United Kingdom

Participants (7)

BEN GURION UNIVERSITY OF THE NEGEV
Israel
Address

84105 Beer Sheva
CANCER RESEARCH UK
United Kingdom
Address
Blanche Lane, Clare Hall Laboratories
EN6 3LD South Mimms
ERASMUS UNIVERSITEIT ROTTERDAM
Netherlands
Address
Dr. Molewaterplein 50
3000 DR Rotterdam
INSTITUT CURIE
France
Address
Rue D' Ulm 26
75248 Paris
UNIVERSITY OF GENEVA
Switzerland
Address
30,Quai Ernest Ausermet 30
1211 Geneve
UNIVERSITY OF SUSSEX
United Kingdom
Address
Falmer
BN1 9RR Brighton / Falmer
UNIVERSITÀ DEGLI STUDI DI MILANO-BICOCCA
Italy
Address
Piazza Della Scienza 2
20126 Milano