title: Cyclin B3 and dynein heavy chain cooperate to increase fitness in the absence of mdf-1/MAD1 in Caenorhabditis elegans.
abstract: Spindle assembly checkpoint (SAC) ensures genome stability by delaying anaphase onset until all the chromosomes have achieved proper spindle attachment. Once correct attachment has been achieved, SAC must be silenced. In the absence of mdf-1/MAD1, an essential SAC component, Caenorhabditis elegans cannot propagate beyond 3 generations. Previously, in a dog-1(gk10)/FANCJ mutator background, we isolated a suppressor of mdf-1(gk2) sterility (such-4) which allowed indefinite propagation in the absence of MDF-1. We showed that such-4 is a Cyclin B3 (cyb-3) duplication. Here we analyze mdf-1 such-4; dog-1, which we propagated for 470 generations, with freezing of samples for long time storage at F170 and F270. Phenotypic analysis of this strain revealed additional suppression of sterility in the absence of MDF-1, beyond the effects of such-4. We applied oligonucleotide array Comparative Genomic Hybridization (oaCGH) and whole genome sequencing (WGS) and identified a further amplification of cyb-3 (triplication) and a new missense mutation in dynein heavy chain (dhc-1). We show that dhc-1(dot168) suppresses the mdf-1(gk2), and is the second cloned suppressor, next to cyb-3 duplication, that does not cause a delay in anaphase onset. We also show that amplification of cyb-3 and dhc-1(dot168) cooperate to increase fitness in the absence of MDF-1.
authors.affiliation: a Department of Molecular Biology and Biochemistry ; Simon Fraser University ; Burnaby , BC Canada.
authors.forename: Maja
authors.initials: M
authors.lastname: Tarailo-Graovac
authors.forename: Tammy
authors.initials: T
authors.lastname: Wong
authors.forename: Zhaozhao
authors.initials: Z
authors.lastname: Qin
authors.forename: Stephane
authors.initials: S
authors.lastname: Flibotte
authors.forename: Jon
authors.initials: J
authors.lastname: Taylor
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rose
authors.forename: Nansheng
authors.initials: N
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000705:Anaphase; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016415:Sequence Alignment
chemical_list: C491028:CYB-3 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; C412839:MDF-1 protein, C elegans; D009687:Nuclear Proteins; D004265:DNA Helicases; C464789:Dog-1 protein, C elegans; D056445:Cytoplasmic Dyneins; C502824:DHC-1 protein, C elegans
keywords: APC/C, anaphase promoting complex/cyclosome; CIN, chromosome instability; Cyclin B3 (cyb-3); EMS, ethyl methanesulfonate; Him, high incidence of males; SAC, spindle assembly checkpoint; WGS, whole genome sequencing; dynein heavy chain (dhc-1); genome stability; mdf-1/MAD1; oaCGH, oligonucleotide array Comparative Genomic Hybridization; spindle assembly checkpoint (SAC)