Nuclear
architecture and double strand breaks repair in yeast subtelomeres.
Emmanuelle Fabre,
Cécile Fairhed, Bernard Dujon
Structure/Dynamics of Genomes, Institut Pasteur, 25 rue du Dr. Roux, Paris,
75015, France (efabre@pasteur.fr)
Little is known about the influence of nuclear architecture on the fate of double strand breaks (DSB) in eukaryotic genomes. To address this question, we have focused our study on DSB repair in yeast subtelomeres. We have indeed previously shown that, contrary to the central regions of a chromosome in which DSB are repaired by non-homologous end joining (NHEJ), alternative modes of repair appear in subtelomeric regions generating new genomic combinations. On the other hand, it is known that chromosome ends are clustered in close proximity to the nuclear periphery and mutants that disrupt the nuclear periphery, including nuclear pore proteins, affect telomeric clustering. Thus yeast chromosomes are probably organised in the nucleus and there have been hints that repair might be linked to this. We have therefore analysed how DSBs were repaired in a nuclear pore protein mutant, nup145ΔC. We used a system where double strand breaks are conditionally induced at specific loci by the I-SceI endonuclease. We found that survival to double strand break was dramatically decreased in this mutated context. However, when repair of double strand breaks can occur, the repair event is similar to the one observed in a wild type context. This suggests that instead of the mode of repair, it is an early processing step that is affected. The regulatory role of this nuclear pore protein on double strand break recognition is currently under study.