title: Ionizing irradiation-induced radical stress stalls live meiotic chromosome movements by altering the actin cytoskeleton.
abstract: Meiosis generates haploid cells or spores for sexual reproduction. As a prelude to haploidization, homologous chromosomes pair and recombine to undergo segregation during the first meiotic division. During the entire meiotic prophase of the yeast Saccharomyces cerevisiae, chromosomes perform rapid movements that are suspected to contribute to the regulation of recombination. Here, we investigated the impact of ionizing radiation (IR) on movements of GFP-tagged bivalents in live pachytene cells. We find that exposure of sporulating cultures with >40 Gy (4-krad) X-rays stalls pachytene chromosome movements. This identifies a previously undescribed acute radiation response in yeast meiosis, which contrasts with its reported radioresistance of up to 1,000 Gy in survival assays. A modified 3'-end labeling assay disclosed IR-induced dsDNA breaks (DSBs) in pachytene cells at a linear dose relationship of one IR-induced DSB per cell per 5 Gy. Dihydroethidium staining revealed formation of reactive oxygen species (ROS) in irradiated cells. Immobility of fuzzy-appearing irradiated bivalents was rescued by addition of radical scavengers. Hydrogen peroxide-induced ROS did reduce bivalent mobility similar to 40 Gy X IR, while they failed to induce DSBs. IR- and H2O2-induced ROS were found to decompose actin cables that are driving meiotic chromosome mobility, an effect that could be rescued by antioxidant treatment. Hence, it appears that the meiotic actin cytoskeleton is a radical-sensitive system that inhibits bivalent movements in response to IR- and oxidant-induced ROS. This may be important to prevent motility-driven unfavorable chromosome interactions when meiotic recombination has to proceed in genotoxic environments.
authors.affiliation: Institut für Radiobiologie der Bundeswehr in Verbindung mit der Universität Ulm, D-80937 Munich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Illner
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology* / Q000528:radiation effects; D002875:Chromosomes / Q000502:physiology* / Q000528:radiation effects; D005453:Fluorescence; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008540:Meiosis / Q000502:physiology* / Q000528:radiation effects; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013172:Spores, Fungal / Q000502:physiology; D018709:Statistics, Nonparametric; D014965:X-Rays
chemical_list: D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; D006861:Hydrogen Peroxide
keywords: ZIP1; low dose radiation response; radical formation; rapid chromosome movements; sporulation
references.citation: Cell. 2008 Jun 27;133(7):1188-201
references.pmid: 18585353
references.citation: Genetics. 1985 Jun;110(2):187-216
references.pmid: 3891509
references.citation: Curr Opin Genet Dev. 2009 Apr;19(2):105-12
references.pmid: 19328674
references.citation: Mutat Res. 1982 Feb 22;92(1-2):229-41
references.pmid: 7088004
references.citation: Chest. 1997 Jul;112(1):164-72
references.pmid: 9228372
references.citation: Cell. 1997 Feb 7;88(3):375-84
references.pmid: 9039264
references.citation: J Cell Biol. 2000 Oct 2;151(1):95-106
references.pmid: 11018056
references.citation: Cytoskeleton (Hoboken). 2011 Jun;68(6):340-54
references.pmid: 21634027
references.citation: Free Radic Res. 2012 Feb;46(2):147-53
references.pmid: 22126415
references.citation: Int J Radiat Biol. 2000 Jan;76(1):67-75
references.pmid: 10665959
references.citation: Int J Radiat Biol Relat Stud Phys Chem Med. 1977 Apr;31(4):365-75
references.pmid: 324937
references.citation: Mol Gen Genet. 1983;191(2):314-8
references.pmid: 6353166
references.citation: Biochem Biophys Res Commun. 1994 Dec 15;205(2):1151-4
references.pmid: 7802644
references.citation: J Cell Biol. 1992 Nov;119(3):493-501
references.pmid: 1400587
references.citation: Cell. 2001 Jul 13;106(1):59-70
references.pmid: 11461702
references.citation: Mol Gen Genet. 1976 Jan 16;143(2):119-29
references.pmid: 765749
references.citation: Genetics. 1993 May;134(1):29-42
references.pmid: 8514137
references.citation: FEMS Microbiol Rev. 2005 Apr;29(2):361-75
references.pmid: 15808748
references.citation: Genetics. 1998 Mar;148(3):975-88
references.pmid: 9539418
references.citation: Nature. 2008 Jul 24;454(7203):479-85
references.pmid: 18615017
references.citation: J Bacteriol. 1974 Apr;118(1):8-14
references.pmid: 4595206
references.citation: Radiat Res. 1980 Jun;82(3):547-58
references.pmid: 6992192
references.citation: Traffic. 2006 Dec;7(12):1628-42
references.pmid: 17118118
references.citation: Cold Spring Harb Symp Quant Biol. 2000;65:377-82
references.pmid: 12760053
references.citation: Methods Mol Biol. 2010;659:363-77
references.pmid: 20809327
references.citation: Methods Mol Biol. 2011;745:537-48
references.pmid: 21660715
references.citation: Trends Cell Biol. 2009 Dec;19(12):716-24
references.pmid: 19854056
references.citation: Radiat Res. 1991 Aug;127(2):171-6
references.pmid: 1947001
references.citation: Mol Biol Cell. 2007 Apr;18(4):1359-65
references.pmid: 17287397
references.citation: Cell Cycle. 2011 Apr 1;10(7):1073-85
references.pmid: 21406975
references.citation: Cancer Res. 2001 May 15;61(10):3894-901
references.pmid: 11358802
references.citation: Genetics. 2002 Jan;160(1):49-62
references.pmid: 11805044
references.citation: Nucleic Acids Res. 1979 Oct 10;7(3):793-804
references.pmid: 92010
references.citation: Cell. 1991 Sep 20;66(6):1239-56
references.pmid: 1913808
references.citation: Nat Genet. 2001 Dec;29(4):426-34
references.pmid: 11726929
references.citation: CSH Protoc. 2006 Jun 01;2006(1):
references.pmid: 22485569
references.citation: Nature. 1976 Apr 8;260(5551):534-5
references.pmid: 1264213
references.citation: Differentiation. 2008 Jan;76(1):91-8
references.pmid: 17697124
references.citation: Cell. 2008 Jun 27;133(7):1175-87
references.pmid: 18585352
references.citation: PLoS Genet. 2008 Sep 26;4(9):e1000188
references.pmid: 18818741
references.citation: Genome Dyn Stab. 2008 Jan 1;2:81-123
references.pmid: 21927624
references.citation: Genetics. 1983 Aug;104(4):603-18
references.pmid: 6352405
references.citation: J Cell Biol. 2005 Jul 18;170(2):213-23
references.pmid: 16027219
references.citation: PLoS Biol. 2007 Dec;5(12):e324
references.pmid: 18076285
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16934-9
references.pmid: 17939997
references.citation: Mutagenesis. 1986 Mar;1(2):151-5
references.pmid: 3333271
references.citation: Genetics. 1969 Jul;62(3):519-31
references.pmid: 5384484
references.citation: Nat Rev Genet. 2005 Jun;6(6):477-87
references.pmid: 15931171