title: A novel function of DNA repair molecule Nbs1 in terminal differentiation of the lens fibre cells and cataractogenesis.
abstract: The Nbs1 protein, hypomorphic mutant in Nijmegen breakage syndrome (NBS), is a component of the Mre11/Rad50/Nbs1 (M/R/N) complex that acts as a DNA double-strand break sensor and functions in cell cycle checkpoint in response to DNA damage and DNA repair. Here we report that targeted disruption of murine NBS1 gene (Nbn) in the lens alters the M/R/N complex nuclear localization and results in microphthalmia in mice due to reduced proliferation of the lens epithelial cells. Unexpectedly, all Nbn-deficient lenses develop cataracts at an early age due to altered lens fibre cell differentiation, including disruption of normal lens epithelial and fibre cell architecture and incomplete denucleation of fibre cells, and these changes are independent of the p53 pathway. In addition, Nbn-deficient lenses show dysregulated transcription of various crystallins. Thus, this study implicates a novel function of Nbs1 in terminal differentiation of the lens fibre cells and in cataractogenesis.
authors.affiliation: International Agency for Research on Cancer (IARC), 150 cours Albert-Thomas, 69008 Lyon, France.
authors.forename: Yun-Gui
authors.initials: YG
authors.lastname: Yang
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Frappart
authors.forename: Lucien
authors.initials: L
authors.lastname: Frappart
authors.forename: Zhao-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Tong
mesh_terms: D000818:Animals; D002386:Cataract / Q000209:etiology* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C466108:Nijmegen breakage syndrome 1 protein, mouse; D009687:Nuclear Proteins