title: Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation.
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.
authors.affiliation: Andalusian Center for Developmental Biology (CABD), CSIC/Junta de Andalucia/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Georgina
authors.initials: G
authors.lastname: Gómez-Saldivar
authors.affiliation: Biology Department, Fairfield University, Fairfield, Connecticut, United States of America.
authors.forename: Anita
authors.identifier: 0000-0002-5738-2260
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Biology Department, Fairfield University, Fairfield, Connecticut, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Mauro
authors.affiliation: Biology Department, Fairfield University, Fairfield, Connecticut, United States of America.
authors.forename: Allison
authors.initials: A
authors.lastname: Lai
authors.affiliation: Andalusian Center for Developmental Biology (CABD), CSIC/Junta de Andalucia/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.|Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Kobe, Japan.
authors.forename: Tokuko
authors.initials: T
authors.lastname: Haraguchi
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.|Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Kobe, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hiraoka
authors.affiliation: Department of Biology and Center for Genomics and Systems Biology, New York University, New York, New York, United States of America.|New York University, Abu Dhabi, United Arab Emirates.
authors.forename: Fabio
authors.initials: F
authors.lastname: Piano
authors.affiliation: Andalusian Center for Developmental Biology (CABD), CSIC/Junta de Andalucia/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Peter
authors.identifier: 0000-0003-3192-4428
authors.initials: P
authors.lastname: Askjaer
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D009685:Nuclear Envelope / Q000235:genetics; D022022:Nuclear Pore / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D008941:Spindle Apparatus / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C514979:mel-28 protein, C elegans