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TELOMERES

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Genome wide identification of factors controlling the telomere damage response a...

Genome wide identification of factors controlling the telomere damage response and telomere driven genomic instability. Telomeres are specialized nucleoprotein complexes that protect chromosome ends against recognition as DNA breaks. In somatic cells telomeres shorten every cell division, eventually compromising telomere function. This leads to act... ver más

30/09/2017

NKI AVL

1M€

Presupuesto del proyecto: 1M€

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STICHTING HET NEDERLANDS KANKER INSTITUUTANTO... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2017-09-30 No tenemos la información de la convocatoria

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Líder del proyecto

STICHTING HET NEDERLANDS KANKER INSTITUUTANTO... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Telomeres are specialized nucleoprotein complexes that protect chromosome ends against recognition as DNA breaks. In somatic cells telomeres shorten every cell division, eventually compromising telomere function. This leads to activation of a DNA damage response that induces irreversible growth arrest or cell death and serves to suppress tumorigenesis by preventing outgrowth of incipient cancer cells. Furthermore, by limiting replicative potential, telomere dysfunction contributes to aging. However, deprotected chromosome ends are also subject to DNA repair activities that lead to chromosome end-to-end fusions. Upon cell division these fusions give rise to genomic instability through breakage-fusion-bridge cycles generating complex, unbalanced chromosome rearrangements. Cells with such instable genomes are highly prone to develop into cancer. The mechanisms underlying the telomere damage response and telomere-driven genomic instability are poorly understood. To increase our understanding of the cellular consequences of telomere dysfunction we will perform genome-wide functional genetic screens to identify factors with important roles in the telomere damage response and telomere-driven genomic instability. We will mechanistically study these genes for their role in the cellular response to telomere dysfunction. In addition, we will address if these factors act uniquely at telomeres or also affect the response to DNA lesions. Due to their unbiased nature these screens represent a unique opportunity to obtain highly novel and potentially unsuspected insights in the events following telomere deprotection. This work will lead to significantly increased mechanistic understanding of how dysfunctional telomeres affect genome stability, cancer development and aging, but might also lead to new insights in responses to DNA damage in general. Furthermore our research findings will facilitate development of new therapeutic strategies for inhibiting cancer and aging.

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