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The role of nuclear pore and inner nuclear envelope proteins in the regulation o...

The role of nuclear pore and inner nuclear envelope proteins in the regulation of recombination and repair pathways in budding yeast DNA double strand breaks (DSBs) and telomeres both represent ends of a linear chromosome, and both can lead to dangerous genomic rearrangements. Recent studies in budding yeast suggest that persistent DSBs associate with factors i... ver más

30/06/2012

FMI

174K€

Presupuesto del proyecto: 174K€

Líder del proyecto

Novartis Forschungsstiftung No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2012-06-30 No tenemos la información de la convocatoria

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FMI

174.07K€ | Lider

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Líder del proyecto

Novartis Forschungsstiftung No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 174K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto DNA double strand breaks (DSBs) and telomeres both represent ends of a linear chromosome, and both can lead to dangerous genomic rearrangements. Recent studies in budding yeast suggest that persistent DSBs associate with factors in two perinuclear compartments, at nuclear pores and in the inner nuclear membrane (INM). The stability of short telomeres also involves telomere binding to an INM protein, Mps3, and unequal sister chromatid exchange in the rDNA array is prevented by binding another INM protein, Heh1. In the absence of this anchor, rDNA rings are excised leading to premature senescence. From these studies it is clear that the interaction of chromatin with the nuclear periphery contributes to genome stability, yet many questions remain concerning the relocalization and its functional consequences. Are these interactions part of a common mechanism to stabilize or process breaks? Do they cross-talk with each other or do the anchorage sites provide distinct activities specific to the context of the DSB? This proposal will examine the role of nuclear pore and INM proteins in telomere maintenance, rDNA stability and DSB repair, but comparing the outcome of damage at the three sites in various mutant strains. I will use high resolution fluorescence imaging to observe the movement of a randomly distributed DSB to the INM or to pores, which can be distinguished by use of fluorescent tagging and a nup133 mutation. I will determine which repair pathways are regulated by the pores and by INM factors involved in perinuclear anchoring, and finally will investigate whether common mechanisms regulate DSBs processing and the repression of recombination at telomeres or within the rDNA. Intruiguingly all of the nuclear envelope components implicated in this process have homologues in higher eukaryotic cells, which suggests that these mechanisms may be conserved.

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