Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
15
08
2022
accepted:
12
07
2023
medline:
31
8
2023
pubmed:
29
8
2023
entrez:
29
8
2023
Statut:
epublish
Résumé
The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination, and a wealth of genetic data connects rDNA instability events giving rise to ERCs with shortened life span and other ageing pathologies. However, we understand little about the molecular effects of ERC accumulation. Here, we studied ageing in the presence and absence of ERCs, and unexpectedly found no evidence of gene expression differences that might indicate stress responses or metabolic feedback caused by ERCs. Neither did we observe any global change in the widespread disruption of gene expression that accompanies yeast ageing, altogether suggesting that ERCs are largely inert. Much of the differential gene expression that accompanies ageing in yeast was actually associated with markers of the senescence entry point (SEP), showing that senescence, rather than age, underlies these changes. Cells passed the SEP irrespective of ERCs, but we found the SEP to be associated with copy number amplification of a region of chromosome XII between the rDNA and the telomere (ChrXIIr) forming linear fragments up to approximately 1.8 Mb size, which arise in aged cells due to rDNA instability but through a different mechanism to ERCs. Therefore, although rDNA copy number increases dramatically with age due to ERC accumulation, our findings implicate ChrXIIr, rather than ERCs, as the primary driver of senescence during budding yeast ageing.
Identifiants
pubmed: 37643194
doi: 10.1371/journal.pbio.3002250
pii: PBIOLOGY-D-22-01780
pmc: PMC10464983
doi:
Substances chimiques
DNA, Ribosomal
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3002250Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0423
Pays : United Kingdom
Informations de copyright
Copyright: © 2023 Zylstra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
Mol Cell. 2018 Nov 1;72(3):583-593.e4
pubmed: 30293780
Genome Biol. 2010;11(10):R106
pubmed: 20979621
PLoS Biol. 2023 Aug 29;21(8):e3002245
pubmed: 37643155
Mol Cell Biol. 1999 May;19(5):3848-56
pubmed: 10207108
iScience. 2018 Sep 28;7:96-109
pubmed: 30267689
Science. 1997 Aug 29;277(5330):1313-6
pubmed: 9271578
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9674-9
pubmed: 26195783
Genes Dev. 2018 Aug 1;32(15-16):1075-1084
pubmed: 30042134
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Mol Biol Cell. 2006 Sep;17(9):3848-59
pubmed: 16807355
PLoS Genet. 2011 Mar;7(3):e1002015
pubmed: 21436897
Microb Cell. 2016 Jun 20;3(7):263-274
pubmed: 28357364
J Vis Exp. 2014 Oct 16;(92):e51850
pubmed: 25350605
EMBO J. 2007 Dec 12;26(24):4996-5006
pubmed: 18007593
Nature. 2010 Mar 25;464(7288):513-9
pubmed: 20336133
Cell. 2018 Oct 18;175(3):780-795.e15
pubmed: 30318142
Genetics. 2000 Feb;154(2):543-56
pubmed: 10655210
Elife. 2018 Feb 13;7:
pubmed: 29436367
BMC Bioinformatics. 2009 Feb 03;10:48
pubmed: 19192299
Yeast. 2019 Sep;36(9):525-539
pubmed: 31199875
Methods Enzymol. 2006;409:329-45
pubmed: 16793410
Elife. 2018 Oct 19;7:
pubmed: 30334737
Yeast. 1998 Jul;14(10):953-61
pubmed: 9717241
Mech Ageing Dev. 2021 Jun;196:111480
pubmed: 33831401
Sci Adv. 2018 Feb 07;4(2):eaaq0236
pubmed: 29441364
Genes Dev. 1998 Dec 15;12(24):3821-30
pubmed: 9869636
Genes Dev. 2014 Feb 15;28(4):396-408
pubmed: 24532716
Genome Biol. 2014;15(12):550
pubmed: 25516281
Elife. 2019 Sep 13;8:
pubmed: 31518229
Biochim Biophys Acta. 2014 Jun;1842(6):860-8
pubmed: 24389328
Elife. 2015 Dec 01;4:e08527
pubmed: 26422514
Genome Biol. 2006;7(11):R107
pubmed: 17105650
Science. 2020 Jul 17;369(6501):325-329
pubmed: 32675375
Elife. 2014 Nov 17;3:
pubmed: 25402830
PLoS Genet. 2017 Sep 7;13(9):e1006994
pubmed: 28880866
Elife. 2019 Apr 09;8:
pubmed: 30963997
Nat Biotechnol. 2020 Mar;38(3):276-278
pubmed: 32055031
Curr Biol. 2002 Jan 22;12(2):165-70
pubmed: 11818070
Nature. 2012 Dec 13;492(7428):261-5
pubmed: 23172144
Mol Cell. 2010 Aug 13;39(3):346-59
pubmed: 20705238
Cell Rep. 2019 Jul 9;28(2):408-422.e4
pubmed: 31291577
Science. 2000 Sep 22;289(5487):2126-8
pubmed: 11000115
Mol Biol Cell. 2008 Jan;19(1):352-67
pubmed: 17959824
Cell. 1997 Dec 26;91(7):1033-42
pubmed: 9428525
J Cell Biol. 2000 May 15;149(4):811-24
pubmed: 10811823
Nat Cell Biol. 2009 Jun;11(6):753-60
pubmed: 19465922
Genome Res. 2008 Jan;18(1):13-8
pubmed: 18025267
J Biol Chem. 2003 Oct 24;278(43):41607-17
pubmed: 12904293
Nature. 1959 Jun 20;183(4677):1751-2
pubmed: 13666896
PLoS One. 2016 Dec 1;11(12):e0167394
pubmed: 27907085
Cell. 1984 Dec;39(3 Pt 2):675-82
pubmed: 6096019
Methods Mol Biol. 2007;371:237-48
pubmed: 17634586
Genes Cells. 2011 Apr;16(4):467-77
pubmed: 21401809
Science. 2011 Jun 24;332(6037):1554-7
pubmed: 21700873
Aging (Albany NY). 2022 Jun 29;14(12):4990-5012
pubmed: 35771153
Nat Cell Biol. 2013 Aug;15(8):1008-15
pubmed: 23811686
PLoS Biol. 2019 Dec 3;17(12):e3000471
pubmed: 31794573
Cell Rep. 2013 Dec 26;5(6):1589-99
pubmed: 24332850
Mol Cell Biol. 2020 Oct 26;40(22):
pubmed: 32900821
Genes Dev. 1999 Oct 1;13(19):2570-80
pubmed: 10521401
Genome Res. 2003 Jun;13(6A):1133-45
pubmed: 12799349
Nucleic Acids Res. 2003 Feb 1;31(3):893-8
pubmed: 12560485
Nat Commun. 2020 May 8;11(1):2267
pubmed: 32385287
Genes Cells. 1996 May;1(5):465-74
pubmed: 9078378
Mol Cell. 1999 Apr;3(4):447-55
pubmed: 10230397
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Elife. 2019 Aug 09;8:
pubmed: 31397671
Cell. 2019 Feb 21;176(5):1083-1097.e18
pubmed: 30739799
Genes Cells. 2002 Feb;7(2):99-113
pubmed: 11895475
Biol Cell. 2023 Jan;115(1):e2200023
pubmed: 36117150
Nucleic Acids Res. 2011 Mar;39(4):1336-50
pubmed: 20947565
Elife. 2022 Apr 04;11:
pubmed: 35373738
Mol Biol Cell. 2000 Dec;11(12):4241-57
pubmed: 11102521
PLoS Genet. 2017 Jun 22;13(6):e1006771
pubmed: 28640831
J Gerontol A Biol Sci Med Sci. 2008 Jan;63(1):21-34
pubmed: 18245757
Genes Dev. 1997 Jan 15;11(2):241-54
pubmed: 9009206
Nat Biotechnol. 2017 Apr 11;35(4):316-319
pubmed: 28398311
PLoS Genet. 2019 Apr 18;15(4):e1008103
pubmed: 30998688
Elife. 2019 Jun 03;8:
pubmed: 31157618
Elife. 2020 Jan 07;9:
pubmed: 31909711
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Nat Cell Biol. 2018 Jan;20(1):92-103
pubmed: 29255170
Mol Cell. 2009 Sep 11;35(5):683-93
pubmed: 19748361
Nat Cell Biol. 2013 Aug;15(8):1001-7
pubmed: 23811685
Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt A):2690-2696
pubmed: 29524633
Nat Methods. 2015 Feb;12(2):115-21
pubmed: 25633503
FEMS Yeast Res. 2013 May;13(3):267-76
pubmed: 23336757
Mol Biol Cell. 2004 Mar;15(3):1297-312
pubmed: 14718559
Genetics. 2009 Oct;183(2):413-22, 1SI-13SI
pubmed: 19652178
Science. 2007 Mar 9;315(5817):1411-5
pubmed: 17347440
DNA Repair (Amst). 2018 Nov;71:135-147
pubmed: 30220600
Elife. 2018 Oct 02;7:
pubmed: 30274593
Mol Cell Biol. 1991 Mar;11(3):1222-31
pubmed: 1996088
Nature. 2008 Aug 7;454(7205):728-34
pubmed: 18660802
Mol Cell. 2010 Sep 10;39(5):724-35
pubmed: 20832724
Mob DNA. 2010 Mar 08;1(1):11
pubmed: 20226008
Genetics. 2015 Jun;200(2):505-21
pubmed: 25823445
Epigenetics. 2020 Jan - Feb;15(1-2):85-106
pubmed: 31352858
Aging Cell. 2013 Feb;12(1):67-75
pubmed: 23082874