Gene-targeted CEP164-deficient cells show a ciliation defect with intact DNA repair capacity
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...
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| Published in: | Journal of cell science |
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01-01-2016
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| 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. |
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| AbstractList | 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. |
| Author | Daly, Owen M. Gaboriau, David King, Sinéad Dantas, Tiago J. Karakaya, Kadin Dockery, Peter Morrison, Ciaran G. Krämer, Alwin Lalor, Pierce |
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| Cites_doi | 10.1101/gad.1627708 10.1002/cm.20536 10.1083/jcb.200707181 10.1038/nature02166 10.1016/j.cell.2012.06.028 10.1083/jcb.201012093 10.1371/journal.pgen.1004594 10.4161/cc.8.4.7844 10.1126/science.1231143 10.1038/nmeth.1401 10.1038/nrg2774 10.1083/jcb.201202126 10.1038/sj.embor.7400962 10.1007/s00018-013-1302-8 10.1073/pnas.1401777111 10.1083/jcb.201101005 10.1126/science.1232033 10.1083/jcb.201411070 10.1083/jcb.200802005 10.1016/j.celrep.2013.10.027 10.1016/j.bpj.2012.05.015 10.1093/emboj/17.18.5497 |
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| References | Cong (2021042614213074100_JCS186221C6) 2013; 339 Schmidt (2021042614213074100_JCS186221C18) 2012; 199 Takata (2021042614213074100_JCS186221C22) 1998; 17 Eykelenboom (2021042614213074100_JCS186221C8) 2013; 5 Kobayashi (2021042614213074100_JCS186221C12) 2011; 193 Goetz (2021042614213074100_JCS186221C9) 2010; 11 Dantas (2021042614213074100_JCS186221C7) 2011; 193 Bourke (2021042614213074100_JCS186221C3) 2007; 8 Andersen (2021042614213074100_JCS186221C1) 2003; 426 Graser (2021042614213074100_JCS186221C11) 2007; 179 Slaats (2021042614213074100_JCS186221C21) 2014; 10 Pan (2021042614213074100_JCS186221C16) 2009; 8 Chaki (2021042614213074100_JCS186221C5) 2012; 150 Nishimura (2021042614213074100_JCS186221C15) 2009; 6 Čajanek (2021042614213074100_JCS186221C4) 2014; 111 Prosser (2021042614213074100_JCS186221C17) 2015; 208 Bird (2021042614213074100_JCS186221C2) 2008; 182 Sillibourne (2021042614213074100_JCS186221C19) 2011; 68 Goto (2021042614213074100_JCS186221C10) 2013; 70 Lau (2021042614213074100_JCS186221C13) 2012; 102 Mali (2021042614213074100_JCS186221C14) 2013; 339 Sivasubramaniam (2021042614213074100_JCS186221C20) 2008; 22 |
| References_xml | – volume: 22 start-page: 587 year: 2008 ident: 2021042614213074100_JCS186221C20 article-title: Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1 publication-title: Genes Dev. doi: 10.1101/gad.1627708 contributor: fullname: Sivasubramaniam – volume: 68 start-page: 619 year: 2011 ident: 2021042614213074100_JCS186221C19 article-title: Assessing the localization of centrosomal proteins by PALM/STORM nanoscopy publication-title: Cytoskeleton doi: 10.1002/cm.20536 contributor: fullname: Sillibourne – volume: 179 start-page: 321 year: 2007 ident: 2021042614213074100_JCS186221C11 article-title: Cep164, a novel centriole appendage protein required for primary cilium formation publication-title: J. Cell Biol. doi: 10.1083/jcb.200707181 contributor: fullname: Graser – volume: 426 start-page: 570 year: 2003 ident: 2021042614213074100_JCS186221C1 article-title: Proteomic characterization of the human centrosome by protein correlation profiling publication-title: Nature doi: 10.1038/nature02166 contributor: fullname: Andersen – volume: 150 start-page: 533 year: 2012 ident: 2021042614213074100_JCS186221C5 article-title: Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling publication-title: Cell doi: 10.1016/j.cell.2012.06.028 contributor: fullname: Chaki – volume: 193 start-page: 307 year: 2011 ident: 2021042614213074100_JCS186221C7 article-title: Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins publication-title: J. Cell Biol. doi: 10.1083/jcb.201012093 contributor: fullname: Dantas – volume: 10 start-page: e1004594 year: 2014 ident: 2021042614213074100_JCS186221C21 article-title: Nephronophthisis-associated CEP164 regulates cell cycle progression, apoptosis and epithelial-to-mesenchymal transition publication-title: PLoS Genet. doi: 10.1371/journal.pgen.1004594 contributor: fullname: Slaats – volume: 8 start-page: 655 year: 2009 ident: 2021042614213074100_JCS186221C16 article-title: UV-dependent interaction between Cep164 and XPA mediates localization of Cep164 at sites of DNA damage and UV sensitivity publication-title: Cell Cycle doi: 10.4161/cc.8.4.7844 contributor: fullname: Pan – volume: 339 start-page: 819 year: 2013 ident: 2021042614213074100_JCS186221C6 article-title: Multiplex genome engineering using CRISPR/Cas systems publication-title: Science doi: 10.1126/science.1231143 contributor: fullname: Cong – volume: 6 start-page: 917 year: 2009 ident: 2021042614213074100_JCS186221C15 article-title: An auxin-based degron system for the rapid depletion of proteins in nonplant cells publication-title: Nat. Methods doi: 10.1038/nmeth.1401 contributor: fullname: Nishimura – volume: 11 start-page: 331 year: 2010 ident: 2021042614213074100_JCS186221C9 article-title: The primary cilium: a signalling centre during vertebrate development publication-title: Nat. Rev. Genet. doi: 10.1038/nrg2774 contributor: fullname: Goetz – volume: 199 start-page: 1083 year: 2012 ident: 2021042614213074100_JCS186221C18 article-title: Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis publication-title: J. Cell Biol. doi: 10.1083/jcb.201202126 contributor: fullname: Schmidt – volume: 8 start-page: 603 year: 2007 ident: 2021042614213074100_JCS186221C3 article-title: DNA damage induces Chk1-dependent centrosome amplification publication-title: EMBO Rep. doi: 10.1038/sj.embor.7400962 contributor: fullname: Bourke – volume: 70 start-page: 3893 year: 2013 ident: 2021042614213074100_JCS186221C10 article-title: Cell cycle progression by the repression of primary cilia formation in proliferating cells publication-title: Cell. Mol. Life Sci. doi: 10.1007/s00018-013-1302-8 contributor: fullname: Goto – volume: 111 start-page: E2841 year: 2014 ident: 2021042614213074100_JCS186221C4 article-title: Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1401777111 contributor: fullname: Čajanek – volume: 193 start-page: 435 year: 2011 ident: 2021042614213074100_JCS186221C12 article-title: Regulating the transition from centriole to basal body publication-title: J. Cell Biol. doi: 10.1083/jcb.201101005 contributor: fullname: Kobayashi – volume: 339 start-page: 823 year: 2013 ident: 2021042614213074100_JCS186221C14 article-title: RNA-guided human genome engineering via Cas9 publication-title: Science doi: 10.1126/science.1232033 contributor: fullname: Mali – volume: 208 start-page: 693 year: 2015 ident: 2021042614213074100_JCS186221C17 article-title: Centrin2 regulates CP110 removal in primary cilium formation publication-title: J. Cell Biol. doi: 10.1083/jcb.201411070 contributor: fullname: Prosser – volume: 182 start-page: 289 year: 2008 ident: 2021042614213074100_JCS186221C2 article-title: Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A publication-title: J. Cell Biol. doi: 10.1083/jcb.200802005 contributor: fullname: Bird – volume: 5 start-page: 1095 year: 2013 ident: 2021042614213074100_JCS186221C8 article-title: ATR activates the S-M checkpoint during unperturbed growth to ensure sufficient replication prior to mitotic onset publication-title: Cell Rep. doi: 10.1016/j.celrep.2013.10.027 contributor: fullname: Eykelenboom – volume: 102 start-page: 2926 year: 2012 ident: 2021042614213074100_JCS186221C13 article-title: STED microscopy with optimized labeling density reveals 9-fold arrangement of a centriole protein publication-title: Biophys. J. doi: 10.1016/j.bpj.2012.05.015 contributor: fullname: Lau – volume: 17 start-page: 5497 year: 1998 ident: 2021042614213074100_JCS186221C22 article-title: Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells publication-title: EMBO J. doi: 10.1093/emboj/17.18.5497 contributor: fullname: Takata |
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