title: Chromosome tips damaged in anaphase inhibit cytokinesis.
abstract: Genome maintenance is ensured by a variety of biochemical sensors and pathways that repair accumulated damage. During mitosis, the mechanisms that sense and resolve DNA damage remain elusive. Studies have demonstrated that damage accumulated on lagging chromosomes can activate the spindle assembly checkpoint. However, there is little known regarding damage to DNA after anaphase onset. In this study, we demonstrate that laser-induced damage to chromosome tips (presumptive telomeres) in anaphase of Potorous tridactylis cells (PtK2) inhibits cytokinesis. In contrast, equivalent irradiation of non-telomeric chromosome regions or control irradiations in either the adjacent cytoplasm or adjacent to chromosome tips near the spindle midzone during anaphase caused no change in the eventual completion of cytokinesis. Damage to only one chromosome tip caused either complete absence of furrow formation, a prolonged delay in furrow formation, or furrow regression. When multiple chromosome tips were irradiated in the same cell, the cytokinesis defects increased, suggesting a potential dose-dependent mechanism. These results suggest a mechanism in which dysfunctional telomeres inhibit mitotic exit.
authors.affiliation: Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Norman M
authors.initials: NM
authors.lastname: Baker
authors.forename: Samantha G
authors.initials: SG
authors.lastname: Zeitlin
authors.forename: Linda Z
authors.initials: LZ
authors.lastname: Shi
authors.forename: Jagesh
authors.initials: J
authors.lastname: Shah
authors.forename: Michael W
authors.initials: MW
authors.lastname: Berns
mesh_terms: D000705:Anaphase / Q000235:genetics* / Q000528:radiation effects; D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations / Q000528:radiation effects; D002875:Chromosomes / Q000235:genetics* / Q000528:radiation effects; D048749:Cytokinesis / Q000235:genetics* / Q000528:radiation effects; D004249:DNA Damage; D007834:Lasers; D048328:Potoroidae; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D016615:Telomere / Q000235:genetics
references.citation: Microsc Res Tech. 2005 Oct;68(2):65-74
references.pmid: 16228982
references.citation: Curr Biol. 2003 Sep 2;13(17):1549-56
references.pmid: 12956959
references.citation: Cell. 2009 Feb 6;136(3):473-84
references.pmid: 19203582
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12903-8
references.pmid: 18723675
references.citation: J Biomed Opt. 2007 Mar-Apr;12(2):020505
references.pmid: 17477704
references.citation: J Cell Biol. 1990 Oct;111(4):1505-18
references.pmid: 2211823
references.citation: Nature. 2009 Oct 22;461(7267):1071-8
references.pmid: 19847258
references.citation: J Cell Sci. 1995 Jul;108 ( Pt 7):2537-48
references.pmid: 7593295
references.citation: Methods Cell Biol. 2007;82:1-58
references.pmid: 17586253
references.citation: J Cell Biol. 1994 Dec;127(5):1301-10
references.pmid: 7962091
references.citation: J Cell Biol. 1995 Aug;130(4):941-8
references.pmid: 7642709
references.citation: Science. 2004 Apr 2;304(5667):97-100
references.pmid: 15064417
references.citation: J Cell Biol. 2008 Oct 6;183(1):29-36
references.pmid: 18824563
references.citation: Nat Genet. 2008 Mar;40(3):362-6
references.pmid: 18246067
references.citation: Mol Cell. 2004 Sep 24;15(6):977-90
references.pmid: 15383286
references.citation: Opt Lett. 1991 Oct 1;16(19):1463-5
references.pmid: 19777001
references.citation: Nucleic Acids Res. 2009 May;37(9):e68
references.pmid: 19357094
references.citation: Biophys J. 2004 Dec;87(6):4203-12
references.pmid: 15454403
references.citation: J Cell Biol. 1996 Nov;135(4):981-9
references.pmid: 8922381
references.citation: Cell. 2010 Apr 2;141(1):81-93
references.pmid: 20371347
references.citation: Curr Biol. 2010 Mar 23;20(6):521-6
references.pmid: 20226664
references.citation: Nat Rev Mol Cell Biol. 2009 Jul;10(7):478-87
references.pmid: 19546858
references.citation: Genes Dev. 2010 Apr 1;24(7):720-33
references.pmid: 20360388
references.citation: Curr Biol. 2002 Oct 29;12(21):1797-806
references.pmid: 12419179
references.citation: Cytogenet Genome Res. 2008;122(3-4):365-73
references.pmid: 19188707
references.citation: Carcinogenesis. 2010 Jan;31(1):59-70
references.pmid: 19875697
references.citation: Nature. 2003 Nov 13;426(6963):194-8
references.pmid: 14608368
references.citation: J Cell Biol. 1997 Jan 27;136(2):229-40
references.pmid: 9015296