title: The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans.
abstract: Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole . Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Jacqueline G
authors.identifier: http://orcid.org/0000-0002-1357-4551
authors.initials: JG
authors.lastname: Miller
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Yan
authors.identifier: http://orcid.org/0000-0003-4473-2337
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Christopher W
authors.identifier: http://orcid.org/0000-0002-6086-7859
authors.initials: CW
authors.lastname: Williams
authors.affiliation: Genomics Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Harold E
authors.identifier: http://orcid.org/0000-0002-3517-5973
authors.initials: HE
authors.lastname: Smith
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 kevino@mail.nih.gov.
authors.forename: Kevin F
authors.identifier: http://orcid.org/0000-0002-9789-288X
authors.initials: KF
authors.lastname: O'Connell
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002502:Centrioles / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D005804:Genes, Lethal; D049751:Genome, Helminth; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation; D050680:Transcription Factor DP1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D050684:E2F Transcription Factors; D046912:Multiprotein Complexes; D050680:Transcription Factor DP1
keywords: C. elegans; E2F/DP1; SAS-6; centriole duplication; transcriptional regulation