Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation

Georgina Gómez-Saldivar, Anita Fernandez, Yasuhiro Hirano, Michael Mauro, Allison Lai, Cristina Ayuso, Tokuko Haraguchi, Yasushi Hiraoka, Fabio Piano, Peter Askjaer

Research output: Contribution to journalArticle

Abstract

Nucleoporins are the constituents of nuclear pore complexes (NPCs) and are essential regulators of nucleocytoplasmic transport, gene expression and genome stability. The nucleoporin MEL-28/ELYS plays a critical role in post-mitotic NPC reassembly through recruitment of the NUP107-160 subcomplex, and is required for correct segregation of mitotic chromosomes. Here we present a systematic functional and structural analysis of MEL-28 in C. elegans early development and human ELYS in cultured cells. We have identified functional domains responsible for nuclear envelope and kinetochore localization, chromatin binding, mitotic spindle matrix association and chromosome segregation. Surprisingly, we found that perturbations to MEL-28’s conserved AT-hook domain do not affect MEL-28 localization although they disrupt MEL-28 function and delay cell cycle progression in a DNA damage checkpoint-dependent manner. Our analyses also uncover a novel meiotic role of MEL-28. Together, these results show that MEL-28 has conserved structural domains that are essential for its fundamental roles in NPC assembly and chromosome segregation.

Original languageEnglish (US)
Article numbere1006131
JournalPLoS genetics
Volume12
Issue number6
DOIs
StatePublished - Jun 2016

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Gómez-Saldivar, G., Fernandez, A., Hirano, Y., Mauro, M., Lai, A., Ayuso, C., Haraguchi, T., Hiraoka, Y., Piano, F., & Askjaer, P. (2016). Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation. PLoS genetics, 12(6), [e1006131]. https://doi.org/10.1371/journal.pgen.1006131