Human chromosome-specific aneuploidy is influenced by DNA-dependent centromeric features.
CENP
CENP-B boxes
aneuploidy
centromere
chromosome segregation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
12
07
2019
revised:
21
10
2019
accepted:
29
10
2019
pubmed:
22
11
2019
medline:
14
7
2020
entrez:
22
11
2019
Statut:
ppublish
Résumé
Intrinsic genomic features of individual chromosomes can contribute to chromosome-specific aneuploidy. Centromeres are key elements for the maintenance of chromosome segregation fidelity via a specialized chromatin marked by CENP-A wrapped by repetitive DNA. These long stretches of repetitive DNA vary in length among human chromosomes. Using CENP-A genetic inactivation in human cells, we directly interrogate if differences in the centromere length reflect the heterogeneity of centromeric DNA-dependent features and whether this, in turn, affects the genesis of chromosome-specific aneuploidy. Using three distinct approaches, we show that mis-segregation rates vary among different chromosomes under conditions that compromise centromere function. Whole-genome sequencing and centromere mapping combined with cytogenetic analysis, small molecule inhibitors, and genetic manipulation revealed that inter-chromosomal heterogeneity of centromeric features, but not centromere length, influences chromosome segregation fidelity. We conclude that faithful chromosome segregation for most of human chromosomes is biased in favor of centromeres with high abundance of DNA-dependent centromeric components. These inter-chromosomal differences in centromere features can translate into non-random aneuploidy, a hallmark of cancer and genetic diseases.
Identifiants
pubmed: 31750958
doi: 10.15252/embj.2019102924
pmc: PMC6960447
doi:
Substances chimiques
Centromere Protein A
0
Chromatin
0
DNA
9007-49-2
Banques de données
GEO
['GSE132193']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e102924Subventions
Organisme : ATIP-Avenir
ID : ANR-10-LABX-0038
Pays : International
Organisme : ATIP-Avenir
ID : ANR-10-IDEX-0001-02
Pays : International
Organisme : Emergence
Pays : International
Organisme : AIRC post-doctoral fellowship for abroad research
Pays : International
Organisme : National Science Foundation CAREER Award
ID : 1652512
Pays : International
Organisme : Dutch Cancer Society
Pays : International
Informations de copyright
© 2019 The Authors.
Références
Nat Rev Genet. 2012 Jan 24;13(3):189-203
pubmed: 22269907
Genome Res. 2017 May;27(5):849-864
pubmed: 28396521
Nat Commun. 2018 May 23;9(1):2042
pubmed: 29795284
Front Genet. 2018 Dec 21;9:674
pubmed: 30627137
Nature. 2019 May;569(7757):503-508
pubmed: 31068700
Aging (Albany NY). 2010 Nov;2(11):785-90
pubmed: 21068465
Dev Cell. 2015 May 4;33(3):314-27
pubmed: 25942623
Genome Biol. 2016 May 31;17(1):115
pubmed: 27246460
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
J Cell Biol. 1992 Feb;116(3):585-96
pubmed: 1730770
Nat Biotechnol. 2004 Dec;22(12):1583-7
pubmed: 15568020
Stem Cell Reports. 2017 Jun 6;8(6):1675-1688
pubmed: 28591650
Genome Res. 2016 Oct;26(10):1301-1311
pubmed: 27510565
Elife. 2015 Jun 16;4:e09225
pubmed: 26079792
Nat Rev Mol Cell Biol. 2015 Aug;16(8):473-85
pubmed: 26204159
Biomolecules. 2019 Jan 26;9(2):
pubmed: 30691136
EMBO J. 2020 Jan 2;39(1):e101112
pubmed: 31721251
Cancer Res. 2005 Mar 15;65(6):2139-46
pubmed: 15781624
Prog Mol Subcell Biol. 2017;56:285-304
pubmed: 28840242
Elife. 2017 Jan 16;6:
pubmed: 28079019
Cell. 2019 Aug 22;178(5):1132-1144.e10
pubmed: 31402175
Lancet. 1996 May 4;347(9010):1222-5
pubmed: 8622452
Semin Cancer Biol. 2008 Apr;18(2):123-30
pubmed: 18291669
Nature. 2011 Aug 28;477(7364):354-8
pubmed: 21874020
Science. 2006 Jan 20;311(5759):388-91
pubmed: 16424343
Nat Rev Genet. 2012 Jun 18;13(7):493-504
pubmed: 22705668
Trends Genet. 2004 Nov;20(11):529-33
pubmed: 15475110
Genes Chromosomes Cancer. 1995 Aug;13(4):229-38
pubmed: 7547630
J Cell Sci. 1993 Feb;104 ( Pt 2):261-74
pubmed: 8505360
Cell. 2009 May 1;137(3):472-84
pubmed: 19410544
Teratog Carcinog Mutagen. 1996;16(5):243-52
pubmed: 9122890
Hum Genet. 2017 May;136(5):657-663
pubmed: 28424864
Genes Chromosomes Cancer. 2019 Jun;58(6):392-395
pubmed: 30411433
Nat Genet. 2019 May;51(5):824-834
pubmed: 31036964
Dev Cell. 2014 Sep 8;30(5):496-508
pubmed: 25203206
Nature. 2016 Sep 8;537(7619):249-253
pubmed: 27580032
Genome Res. 2014 Apr;24(4):697-707
pubmed: 24501022
Cell. 2009 May 1;137(3):485-97
pubmed: 19410545
Cell Rep. 2018 Jun 12;23(11):3366-3380
pubmed: 29898405
Nucleus. 2017 Jul 4;8(4):331-339
pubmed: 28406740
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Chromosome Res. 2004;12(8):805-15
pubmed: 15702419
Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):3002-7
pubmed: 25713381
PLoS Biol. 2007 Sep 4;5(10):e254
pubmed: 17803354
Lancet. 1961 Mar 25;1(7178):638-40
pubmed: 13698902
J Cell Biol. 2019 Aug 5;218(8):2492-2513
pubmed: 31270138
Sci Adv. 2015 Feb 12;1(1):null
pubmed: 25927077
Nature. 2002 May 16;417(6886):227
pubmed: 12015578
Chromosoma. 2001 Aug;110(4):253-66
pubmed: 11534817
Mutagenesis. 2014 Nov;29(6):447-55
pubmed: 25217771
PLoS One. 2017 Jun 22;12(6):e0179514
pubmed: 28640891
Int J Cancer. 2013 May 15;132(10):2316-26
pubmed: 23124507
Curr Biol. 2014 Oct 6;24(19):2295-300
pubmed: 25242031
Nat Biotechnol. 2016 May;34(5):528-30
pubmed: 27088723
EMBO J. 1999 Aug 2;18(15):4196-209
pubmed: 10428958
Cells. 2019 Aug 16;8(8):
pubmed: 31426433
Nat Cell Biol. 2019 Jun;21(6):743-754
pubmed: 31160708
Elife. 2016 Dec 24;5:
pubmed: 28012276
FEBS J. 2005 Jan;272(1):282-9
pubmed: 15634350
Curr Biol. 2018 May 7;28(9):1344-1356.e5
pubmed: 29706521
Bioinformatics. 2014 Mar 1;30(5):614-20
pubmed: 24142950
Nat Genet. 2014 Jun;46(6):624-8
pubmed: 24777449
Nature. 2006 May 4;441(7089):46-52
pubmed: 16541025
Cold Spring Harb Symp Quant Biol. 2017;82:249-257
pubmed: 29440567
Cell Rep. 2016 Nov 22;17(9):2394-2404
pubmed: 27880912
Nat Cell Biol. 2017 Jan;19(1):68-75
pubmed: 27918550
Nat Cell Biol. 2006 May;8(5):458-69
pubmed: 16622419
J Cell Biol. 1987 Apr;104(4):817-29
pubmed: 2435739
Cell Syst. 2016 Oct 26;3(4):385-394.e3
pubmed: 27693023
J Cell Biol. 2017 Mar 6;216(3):607-621
pubmed: 28235947
Curr Biol. 2017 Aug 7;27(15):2365-2373.e8
pubmed: 28756949
Chromosoma. 1989 Jun;98(1):1-12
pubmed: 2475307
Cell Cycle. 2014;13(5):739-48
pubmed: 24362315
Genome Res. 2017 Dec;27(12):2040-2049
pubmed: 29141960
Nature. 2012 Jan 18;482(7383):53-8
pubmed: 22258507
Mutagenesis. 1998 May;13(3):235-41
pubmed: 9643581
Bioinformatics. 2011 Mar 15;27(6):764-70
pubmed: 21217122
Nat Cell Biol. 2013 Sep;15(9):1056-66
pubmed: 23873148
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Prog Mol Subcell Biol. 2017;56:305-336
pubmed: 28840243
Invest Ophthalmol Vis Sci. 2001 Oct;42(11):2472-7
pubmed: 11581185
Nature. 2018 Jul;559(7714):350-355
pubmed: 29995854
Chromosome Res. 2011 May;19(4):457-70
pubmed: 21484447
Science. 2015 Jan 2;347(6217):81-3
pubmed: 25477213
Cytometry. 1993;14(4):362-8
pubmed: 8513693
Prog Mol Subcell Biol. 2017;56:377-396
pubmed: 28840246