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The role of nuclear pore and inner nuclear envelope proteins in the regulation of recombination and repair pathways in budding yeast

Project information

Grant agreement ID: 254779

Status

Closed project

  • Start date

    1 July 2010

  • End date

    30 June 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 174 065,20

  • EU contribution

    € 174 065,20

Coordinated by:

Novartis Forschungsstiftung

Switzerland

Objective

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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Coordinator

Novartis Forschungsstiftung

Address

Maulbeerstrasse 66
4058 Basel

Switzerland

Activity type

Research Organisations

EU Contribution

€ 174 065,20

Administrative Contact

Dorothy Searles (Ms.)

Project information

Grant agreement ID: 254779

Status

Closed project

  • Start date

    1 July 2010

  • End date

    30 June 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 174 065,20

  • EU contribution

    € 174 065,20

Coordinated by:

Novartis Forschungsstiftung

Switzerland