title: Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories.
abstract: Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.
authors.affiliation: Section of Cancer Genomics, Genetics Branch, National Cancer Institute, and.
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.affiliation: Section of Cancer Genomics, Genetics Branch, National Cancer Institute, and.
authors.forename: Darawalee
authors.initials: D
authors.lastname: Wangsa
authors.affiliation: Section of Cancer Genomics, Genetics Branch, National Cancer Institute, and.
authors.forename: Martin
authors.initials: M
authors.lastname: Falke
authors.affiliation: Section of Cancer Genomics, Genetics Branch, National Cancer Institute, and.
authors.forename: Markus
authors.initials: M
authors.lastname: Brown
authors.affiliation: Section of Cancer Genomics, Genetics Branch, National Cancer Institute, and.
authors.forename: Chanelle M
authors.initials: CM
authors.lastname: Case
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, U.S. National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Erdos
authors.affiliation: Section of Cancer Genomics, Genetics Branch, National Cancer Institute, and riedt@mail.nih.gov.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure; D002887:Chromosomes, Human, Pair 18 / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19 / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000473:pathology; D006570:Heterochromatin / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D034921:Lamin Type B / Q000172:deficiency / Q000502:physiology*; D008745:Methylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D059506:Telomere Shortening / Q000187:drug effects
chemical_list: D006570:Heterochromatin; D006657:Histones; D034921:Lamin Type B; D034741:RNA, Small Interfering
keywords: alternative splicing; nuclear organization
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