Should I stay or should I go?

Speaker: Anna Marzellíusardóttir, PhD Student. Supervisor, Yves Barral, Institute of Biochemistry, ETH Zürich.

Title: Should I stay or should I go? The role of the chromosome condensation pathway in distinguishing chromosomes from extrachromosomal DNA.

Abstract: In addition to chromosomes, cells can harbour various other DNA species such as extrachromosomal circular DNA (eccDNA). EccDNA can be found in all eukaryotes, and in the budding yeast S. cerevisiae extrachromosomal rDNA circles (ERCs) are the most abundant. While chromosomes are symmetrically segregated between mother and daughter cells in mitosis, ERCs are asymmetrically retained in the mother cell by being tethered to nuclear pore complexes (NPCs). Like ERCs, chromosomes interact extensively with NPCs and other factors at the nuclear envelope (NE). Previous studies have shown that in contrast to ERCs, chromosomes need to detach from the NE prior to mitosis in order to be properly segregated. But how cells distinguish between chromosomes and ERCs in mitosis is not known. Interestingly, NPCs bound by DNA circles lack the nucleoplasmic basket, which has been previously shown to be important for recruiting chromatin to NPCs. We found, however, that when the NPC basket protein Nup60 or the NPC associated ubiquitin ligase Slx5 are deleted, chromosomes are not only closer to the NE but are also increasingly mis-segregated. In addition, tethering Nup60 or Slx5 to DNA circles causes them to be released from NPCs and randomly segregated. This suggests that these factors facilitate detachment of DNA from NPCs. Interestingly, while chromosomes condense in mitosis, DNA circles do not. Moreover, when DNA circles are forced to condense, they are released from NPCs during mitosis and randomly segregated, indicating that condensation might promote detachment of DNA from the NE and facilitate its symmetric partitioning. Remarkably, we found that Nup60 also has a role in chromosome condensation. Together, our data suggest a novel role for the chromosome condensation pathway and the NPC basket in distinguishing chromosomes from extrachromosomal DNA by liberating chromosomes from mother cell retention and facilitating their symmetric segregation.

Short bio: Anna was born and raised in Ísafjörður, Iceland. In 2013 she obtained a Bachelor's degree in Biology and in 2015 a Master's degree in Biomedical Sciences, both from the University of Iceland. She did her Master's thesis under the supervision of Rósa Barkardóttir at the Laboratory of cell biology at Landspítali University Hospital, where she sought to identify novel breast cancer susceptibility genes using whole genome sequencing (WGS) data from Icelandic breast cancer families. In the fall of 2016, she started her PhD in the laboratory of Yves Barral at ETH Zürich, where she has studied how the budding yeast Saccharomyces cerevisiae distinguishes chromosomal from extrachromosomal DNA.