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Mechanisms of DNA repair by human DNA polymerase lambda

Objetivo

DNA polymerases are essential components of the molecular machinery that replicates and repairs DNA in the cell. Human DNA polymerase lambda (Pol lambda) is a newly discovered polymerase implicated in base excision repair and double-stranded break repair, two processes critically important in assuring genetic stability. Research described in this proposal aims at a structural and functional characterization of Pol lambda in human cells. The objective is to gain understanding about its mechanism of action by application of a range of biochemical and cell biology methodologies. A detailed analysis of the interaction of Pol lambda with proliferating cell nuclear antigen (PCNA) will be complemented with genome-wide search of other repair components that inte ract with Pol lambda. Purified proteins and synthetic DNA templates will be used in ‘ in vitro’ assays with the goal of defining the natural DNA substrates and the kinetic parameters of the repair reactions. The function of Pol lambd a will be further investigated by assaying a variety of cytotoxic agents in cell lines in which expression of Pol lambda can be artificially modulated. Special emphasis will be given to potential role of Pol lambda in tumour development. As part of the Marie Curie Action, the goal of this grant is support for the long-term reintegration of a highly experienced researcher in the European Research Area. The applicant has spent twelve years performing research in biochemistry in highly recognized institutions in the United States, and aims to transfer the gained expertise to a centre of excellence in the European Union. In this regard this proposal directly contributes to the European policy of return of European investigators from abroad, enhancement of th eir mobility, and the fostering of national and international collaborative links among researchers.

Ámbito científico (EuroSciVoc)

Tema(s)

Convocatoria de propuestas

FP6-2004-MOBILITY-12
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Régimen de financiación

IRG - Marie Curie actions-International re-integration grants

Coordinador

CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA, CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Aportación de la UE
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Coste total
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