title: Ccdc13 is a novel human centriolar satellite protein required for ciliogenesis and genome stability.
abstract: Here, we identify coiled-coil domain-containing protein 13 (Ccdc13) in a genome-wide RNA interference screen for regulators of genome stability. We establish that Ccdc13 is a newly identified centriolar satellite protein that interacts with PCM1, Cep290 and pericentrin and prevents the accumulation of DNA damage during mitotic transit. Depletion of Ccdc13 results in the loss of microtubule organisation in a manner similar to PCM1 and Cep290 depletion, although Ccdc13 is not required for satellite integrity. We show that microtubule regrowth is enhanced in Ccdc13-depleted cells, but slowed in cells that overexpress Ccdc13. Furthermore, in serum-starved cells, Ccdc13 localises to the basal body, is required for primary cilia formation and promotes the localisation of the ciliopathy protein BBS4 to both centriolar satellites and cilia. These data highlight the emerging link between DNA damage response factors, centriolar and peri-centriolar satellites and cilia-associated proteins and implicate Ccdc13 as a centriolar satellite protein that functions to promote both genome stability and cilia formation.
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Staples
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Katie N
authors.initials: KN
authors.lastname: Myers
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Ryan D D
authors.initials: RD
authors.lastname: Beveridge
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Abhijit A
authors.initials: AA
authors.lastname: Patil
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Howard
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Barone
authors.affiliation: Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Alvin J X
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
authors.affiliation: High Throughput Screening Facility, CR-UK London Research Institute, 44 Lincoln's Inn Fields London, WC2A 3LY, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.affiliation: Mass Spectrometry Group, The MRC Laboratory of Molecular Biology, Division of Cell Biology, Hills Road, Cambridge, CB2 0QH, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maslen
authors.affiliation: Mass Spectrometry Group, The MRC Laboratory of Molecular Biology, Division of Cell Biology, Hills Road, Cambridge, CB2 0QH, UK.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Skehel
authors.affiliation: DNA CR-UK Damage Response Laboratory, London Research Institute, Clare Hall Laboratories, South Mimms, EN6 3LD, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Boulton
authors.affiliation: Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, Department of Oncology, Academic Unit of Molecular Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK s.collis@sheffield.ac.uk.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Collis
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002502:Centrioles / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D042822:Genomic Instability; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins
keywords: Ccdc13; Centriolar satellites; Ciliogenesis; Genome stability