Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.
In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated. In this study, we show that the SAGA complex mediates the interaction of non-chromosomal DNA circles with nuclear pore complexes (NPCs) and thereby promotes their confinement in the mother cell. Reciprocally, this causes retention and accumulation of NPCs, which affects the organization of ageing nuclei. Thus, SAGA prevents the spreading of DNA circles by linking them to NPCs, but unavoidably causes accumulation of circles and NPCs in the mother cell, and thereby promotes ageing. Together, our data provide a unifying model for the asymmetric segregation of DNA circles and how age affects nuclear organization.
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Annina
A
Denoth-Lippuner
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Marek Konrad
MK
Krzyzanowski
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Catherine
C
Stober
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Yves
Y
Barral
D000705:Anaphase; D002503:Centromere / Q000378:metabolism; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000378:metabolism; D004270:DNA, Circular / Q000378:metabolism*; D004271:DNA, Fungal / Q000378:metabolism; D004058:Diffusion; D046210:Microfluidic Analytical Techniques; D008938:Mitosis; D022022:Nuclear Pore / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
D004270:DNA, Circular; D004271:DNA, Fungal; C507785:SAGA complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators
S. cerevisiae; SAGA; ageing; cell biology; nuclear pores