Regulation of nucleotide excision repair by nuclear lamin b1

The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function...

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Veröffentlicht in:PloS one 2013-07, Vol.8 (7), p.e69169-e69169
Hauptverfasser: Butin-Israeli, Veronika, Adam, Stephen A, Goldman, Robert D
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description The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.
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Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. 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Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23894423</pmid><doi>10.1371/journal.pone.0069169</doi><tpages>e69169</tpages><oa>free_for_read</oa></addata></record>
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subjects Analysis
Apoptosis
Biocompatibility
Biology
Biomedical materials
Cell cycle
Cell Cycle - genetics
Cell Cycle - radiation effects
Cell Cycle Checkpoints - genetics
Cell Cycle Checkpoints - radiation effects
Cell growth
Cell Line, Tumor
Cell Proliferation
Cellular Senescence - genetics
Cellular Senescence - radiation effects
Damage detection
Deoxyribonucleic acid
DNA
DNA damage
DNA Damage - genetics
DNA Damage - radiation effects
DNA Helicases - genetics
DNA repair
DNA Repair - genetics
DNA Repair - physiology
DNA Repair Enzymes - genetics
DNA-Binding Proteins - genetics
Enzyme-Linked Immunosorbent Assay
Fibroblasts
Fluorescent Antibody Technique
Gene expression
Humans
Immunoblotting
Immunoglobulins
Irradiation
Kinases
Lamin Type B - genetics
Lamin Type B - metabolism
Lamins
Molecular biology
Mutation
Nuclei
Nuclei (cytology)
Nucleotide excision repair
Osteosarcoma
Penicillin
Poly-ADP-Ribose Binding Proteins
Proliferating cell nuclear antigen
Proliferating Cell Nuclear Antigen - genetics
Proteins
Radiation damage
Repair
RNA polymerase
Rodents
Senescence
Signaling
Stem cells
Tumor cell lines
Ultraviolet radiation
Ultraviolet Rays
title Regulation of nucleotide excision repair by nuclear lamin b1
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