title: Regulation of nucleotide excision repair by nuclear lamin b1.
abstract: 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.
authors.affiliation: The Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Veronika
authors.initials: V
authors.lastname: Butin-Israeli
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Adam
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldman
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; D034921:Lamin Type B; D000075223:Poly-ADP-Ribose Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes
references.citation: CRC Crit Rev Biochem. 1986;21(1):27-52
references.pmid: 3524991
references.citation: Biochem J. 2011 Jun 15;436(3):527-36
references.pmid: 21615334
references.citation: FASEB J. 2008 Feb;22(2):603-11
references.pmid: 17848622
references.citation: Nature. 2005 Sep 22;437(7058):564-8
references.pmid: 16079796
references.citation: Genes Dev. 2012 Oct 15;26(20):2311-24
references.pmid: 23019125
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5076-81
references.pmid: 20145110
references.citation: Nature. 2003 Nov 13;426(6963):194-8
references.pmid: 14608368
references.citation: J Biol Chem. 2003 Jul 4;278(27):25207-17
references.pmid: 12676962
references.citation: Aging (Albany NY). 2009 Jan;1(1):28-37
references.pmid: 19851476
references.citation: Mol Biol Cell. 2011 Dec;22(23):4683-93
references.pmid: 21976703
references.citation: Hum Mol Genet. 2011 Sep 15;20(18):3537-44
references.pmid: 21659336
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: J Cell Biochem. 2012 Aug;113(8):2607-21
references.pmid: 22422629
references.citation: Cold Spring Harb Perspect Biol. 2010 Nov;2(11):a000547
references.pmid: 20826548
references.citation: Nature. 2003 May 15;423(6937):293-8
references.pmid: 12714972
references.citation: EMBO J. 2012 Mar 7;31(5):1080-94
references.pmid: 22246186
references.citation: Genes Dev. 2008 Feb 1;22(3):297-302
references.pmid: 18245444
references.citation: J Cell Biol. 2009 Sep 21;186(6):835-47
references.pmid: 19797077
references.citation: J Cell Sci. 2008 Apr 1;121(Pt 7):1014-24
references.pmid: 18334554
references.citation: J Cell Biol. 2013 Mar 4;200(5):605-17
references.pmid: 23439683
references.citation: Nat Genet. 2006 Oct;38(10):1114-23
references.pmid: 16951681
references.citation: Cell. 2005 May 6;121(3):387-400
references.pmid: 15882621
references.citation: Nature. 2008 Jun 12;453(7197):948-51
references.pmid: 18463634
references.citation: J Cell Biol. 2011 Feb 7;192(3):401-15
references.pmid: 21282463
references.citation: Eur J Neurol. 2010 Apr;17(4):541-9
references.pmid: 19961535
references.citation: Cell Cycle. 2012 Feb 15;11(4):668-74
references.pmid: 22373527
references.citation: Mol Cells. 2008 Jul 31;26(1):5-11
references.pmid: 18525240
references.citation: J Cell Biol. 1994 Jun;125(6):1201-12
references.pmid: 7911470
references.citation: DNA Repair (Amst). 2007 May 1;6(5):649-57
references.pmid: 17236820
references.citation: Exp Cell Res. 2010 Oct 15;316(17):2747-59
references.pmid: 20599958
references.citation: Genes Dev. 2008 Dec 15;22(24):3409-21
references.pmid: 19141474
references.citation: J Cell Sci. 1994 Jan;107 ( Pt 1):61-7
references.pmid: 8175923
references.citation: Mol Cell Biochem. 2012 Jun;365(1-2):323-32
references.pmid: 22382637
references.citation: Nat Cell Biol. 2011 Oct 03;13(10):1161-9
references.pmid: 21968989
references.citation: Cell. 2012 Jun 22;149(7):1474-87
references.pmid: 22726435
references.citation: Gut. 1999 Nov;45(5):723-9
references.pmid: 10517909
references.citation: Cell. 1987 Nov 6;51(3):383-92
references.pmid: 3311384
references.citation: Genes Dev. 2011 Dec 15;25(24):2579-93
references.pmid: 22155925
references.citation: Curr Opin Cell Biol. 2012 Feb;24(1):71-8
references.pmid: 22192274
references.citation: J Virol. 2010 Apr;84(7):3431-42
references.pmid: 20089643
references.citation: Mol Cell. 2012 Apr 13;46(1):18-29
references.pmid: 22405652
references.citation: Cell Cycle. 2009 Jan 15;8(2):191-4
references.pmid: 19158510
references.citation: Nucleic Acids Res. 1997 Oct 1;25(19):3889-94
references.pmid: 9380513
references.citation: Mol Biol Cell. 2012 Jun;23(11):2066-75
references.pmid: 22496421
references.citation: Am J Pathol. 1993 Jul;143(1):211-20
references.pmid: 8391215
references.citation: Photochem Photobiol. 2011 Nov-Dec;87(6):1230-9
references.pmid: 21883247
references.citation: Annu Rev Biochem. 2005;74:317-53
references.pmid: 15952890
references.citation: J Cell Sci. 2006 Nov 15;119(Pt 22):4644-9
references.pmid: 17062639
references.citation: Nat Cell Biol. 2009 Aug;11(8):973-9
references.pmid: 19597488
references.citation: Biochem Soc Trans. 2009 Aug;37(Pt 4):897-904
references.pmid: 19614615
references.citation: DNA Repair (Amst). 2011 Jul 15;10(7):743-50
references.pmid: 21622031
references.citation: Science. 2011 Dec 23;334(6063):1706-10
references.pmid: 22116031
references.citation: Genome Biol. 2011;12(5):222
references.pmid: 21639948
references.citation: Biochemistry (Mosc). 2011 Jan;76(1):16-23
references.pmid: 21568836
references.citation: Curr Opin Genet Dev. 2008 Feb;18(1):80-6
references.pmid: 18343102