title: An SMC-like protein binds and regulates Caenorhabditis elegans condensins.
abstract: Structural Maintenance of Chromosomes (SMC) family proteins participate in multisubunit complexes that govern chromosome structure and dynamics. SMC-containing condensin complexes create chromosome topologies essential for mitosis/meiosis, gene expression, recombination, and repair. Many eukaryotes have two condensin complexes (I and II); C. elegans has three (I, II, and the X-chromosome specialized condensin IDC) and their regulation is poorly understood. Here we identify a novel SMC-like protein, SMCL-1, that binds to C. elegans condensin SMC subunits, and modulates condensin functions. Consistent with a possible role as a negative regulator, loss of SMCL-1 partially rescued the lethal and sterile phenotypes of a hypomorphic condensin mutant, while over-expression of SMCL-1 caused lethality, chromosome mis-segregation, and disruption of condensin IDC localization on X chromosomes. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis, leading to the speculation that it may inhibit condensin ATPase activity. SMCL-1 homologs are apparent only in the subset of Caenorhabditis species in which the condensin I and II subunit SMC-4 duplicated to create the condensin IDC- specific subunit DPY-27, suggesting that SMCL-1 helps this lineage cope with the regulatory challenges imposed by evolution of a third condensin complex. Our findings uncover a new regulator of condensins and highlight how the duplication and divergence of SMC complex components in various lineages has created new proteins with diverse functions in chromosome dynamics.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
authors.forename: Lucy Fang-I
authors.initials: LF
authors.lastname: Chao
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: Meha
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Thompson
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: John R
authors.identifier: 0000-0001-5267-1672
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.|Department of Biology, College of the Holy Cross, Worcester, MA, United States of America.
authors.forename: Kirsten A
authors.identifier: 0000-0002-4187-931X
authors.initials: KA
authors.lastname: Hagstrom
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008540:Meiosis / Q000235:genetics; D018613:Microscopy, Confocal; D008938:Mitosis / Q000235:genetics; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C090454:DPY-27 protein, C elegans; C544458:Dpy-28 protein, C elegans; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D021122:Protein Subunits; C108312:condensin complexes; D000251:Adenosine Triphosphatases