Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation
published on 24/06/2016
Most animal cells have a nucleus that contains the genetic material: the chromosomes. The nucleus is enclosed by the nuclear envelope, which provides a physical barrier between the chromosomes and the surrounding cytoplasm and enables precisely controlled transport of proteins into and out of the nucleus. Transport occurs through nuclear pore complexes, which consist of multiple copies of ~30 different proteins called nucleoporins. Although the composition of nuclear pore complexes is known, the mechanisms of their assembly and function are still unclear.
We have analyzed the nucleoporin MEL-28/ELYS through a systematic dissection of functional domains both in the nematode Caenorhabditis elegans and in human cells. Interestingly, MEL-28/ELYS localizes not only to nuclear pore complexes, but is also associated with chromosomal structures known as kinetochores during cell division. Our studies have revealed that even small perturbations in MEL-28/ELYS can have dramatic consequences on nuclear pore complex assembly as well as on separation of chromosomes during cell division. Surprisingly, inhibition of MEL-28/ELYS causes cell-cycle delay, suggesting activation of a cellular surveillance system for chromosomal damages. Finally, we conclude that the structural domains of MEL-28/ELYS are conserved from nematodes to humans.