title: Promoter hijack reveals pericentrin functions in mitosis and the DNA damage response.
abstract: Centrosomes, the principal microtubule-organizing centers of animal somatic cells, consist of two centrioles embedded in the pericentriolar material (PCM). Pericentrin is a large PCM protein that is required for normal PCM assembly. Mutations in PCNT cause primordial dwarfism. Pericentrin has also been implicated in the control of DNA damage responses. To test how pericentrin is involved in cell cycle control after genotoxic stress, we disrupted the Pcnt locus in chicken DT40 cells. Pericentrin-deficient cells proceeded through mitosis more slowly, with a high level of monopolar spindles, and were more sensitive to spindle poisons than controls. Centriole structures appeared normal by light and electron microscopy, but the PCM did not recruit γ-tubulin efficiently. Cell cycle delays after ionizing radiation (IR) treatment were normal in pericentrin-deficient cells. However, pericentrin disruption in Mcph1-/- cells abrogated centrosome hyperamplification after IR. We conclude that pericentrin controls genomic stability by both ensuring appropriate mitotic spindle activity and centrosome regulation.
authors: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
authors: Yifan
authors: Y
authors: Wang
authors: Tiago J
authors: TJ
authors: Dantas
authors: Pierce
authors: P
authors: Lalor
authors: Peter
authors: P
authors: Dockery
authors: Ciaran G
authors: CG
authors: Morrison
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics* / Q000378:metabolism; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D002645:Chickens; D004249:DNA Damage; D004260:DNA Repair; D017353:Gene Deletion; D056426:Genetic Loci; D042822:Genomic Instability / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects*; D011401:Promoter Regions, Genetic; D011839:Radiation, Ionizing; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; D030161:Avian Proteins; D018797:Cell Cycle Proteins; D014404:Tubulin; C086178:pericentrin
keywords: DNA damage response; centrosome; checkpoint; mitosis; pericentrin