title: CEP164-null cells generated by genome editing show a ciliation defect with intact DNA repair capacity.
abstract: Primary cilia are microtubule structures that extend from the distal end of the mature, mother centriole. CEP164 is a component of the distal appendages carried by the mother centriole that is required for primary cilium formation. Recent data have implicated CEP164 as a ciliopathy gene and suggest that CEP164 plays some roles in the DNA damage response (DDR). We used reverse genetics to test the role of CEP164 in the DDR. We found that conditional depletion of CEP164 in chicken DT40 cells using an auxin-inducible degron led to no increase in sensitivity to DNA damage induced by ionising or ultraviolet irradiation. Disruption of CEP164 in human retinal pigmented epithelial cells blocked primary cilium formation but did not affect cellular proliferation or cellular responses to ionising or ultraviolet irradiation. Furthermore, we observed no localisation of CEP164 to the nucleus using immunofluorescence microscopy and analysis of multiple tagged forms of CEP164. Our data suggest that CEP164 is not required in the DDR.
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences and National University of Ireland Galway, Galway, Ireland.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Daly
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences and National University of Ireland Galway, Galway, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Gaboriau
authors.affiliation: Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
authors.forename: Kadin
authors.initials: K
authors.lastname: Karakaya
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences and National University of Ireland Galway, Galway, Ireland.
authors.forename: Sinéad
authors.initials: S
authors.lastname: King
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences and National University of Ireland Galway, Galway, Ireland.
authors.forename: Tiago J
authors.initials: TJ
authors.lastname: Dantas
authors.affiliation: Anatomy, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Pierce
authors.initials: P
authors.lastname: Lalor
authors.affiliation: Anatomy, School of Medicine, National University of Ireland Galway, Galway, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Dockery
authors.affiliation: Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
authors.forename: Alwin
authors.initials: A
authors.lastname: Krämer
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences and National University of Ireland Galway, Galway, Ireland Ciaran.Morrison@nuigalway.ie.
authors.forename: Ciaran G
authors.identifier: 0000-0003-2401-7029
authors.initials: CG
authors.lastname: Morrison
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D002645:Chickens; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D000072669:Gene Editing; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: C524694:CEP164 protein, human; D008868:Microtubule Proteins
keywords: CEP164; Centrosome amplification; Ciliopathy; DNA damage response; DNA repair; Primary cilium