Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes.
chromosomal instability
methylglyoxal
proteomics
sister chromatid separation
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
08 Apr 2022
08 Apr 2022
Historique:
received:
26
02
2022
revised:
01
04
2022
accepted:
07
04
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
The accurate segregation of sister chromatids is complex, and errors that arise throughout this process can drive chromosomal instability and tumorigenesis. We recently showed that methylglyoxal (MGO), a glycolytic by-product, can cause chromosome missegregation events in lymphocytes. However, the underlying mechanisms of this were not explored. Therefore, in this study, we utilised shotgun proteomics to identify MGO-modified proteins, and label-free quantitation to measure changes in protein abundance following exposure to MGO. We identified numerous mitotic proteins that were modified by MGO, including those involved in the separation and cohesion of sister chromatids. Furthermore, the protein abundance of Securin, an inhibitor of sister chromatid separation, was increased following treatment with MGO. Cytological examination of chromosome spreads showed MGO prevented sister chromatid separation, which was associated with the formation of complex nuclear anomalies. Therefore, results from this study suggest MGO may drive chromosomal instability by preventing sister chromatid separation.
Identifiants
pubmed: 35456956
pii: ijms23084139
doi: 10.3390/ijms23084139
pmc: PMC9030103
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
Magnesium Oxide
3A3U0GI71G
Pyruvaldehyde
722KLD7415
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Mutagenesis. 2021 Oct 6;36(5):339-348
pubmed: 34297102
Cell Mol Life Sci. 2019 Jan;76(2):381-395
pubmed: 30368549
Science. 2001 Aug 17;293(5533):1320-3
pubmed: 11509732
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Carcinogenesis. 2007 Jan;28(1):81-92
pubmed: 16777988
Eur J Cancer. 2013 Jan;49(2):500-10
pubmed: 22819078
Tumour Biol. 2016 Jan;37(1):749-62
pubmed: 26245990
Eur Rev Med Pharmacol Sci. 2018 Mar;22(6):1665-1671
pubmed: 29630110
Mutagenesis. 2017 Dec 31;32(6):547-560
pubmed: 29165592
Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):17974-8
pubmed: 21997207
Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11355-60
pubmed: 23776203
Environ Mol Mutagen. 2012 May;53(4):311-23
pubmed: 22430981
Nat Rev Mol Cell Biol. 2009 Jul;10(7):478-87
pubmed: 19546858
Nat Genet. 2002 Oct;32(2):273-9
pubmed: 12244315
Mutagenesis. 2020 Sep 12;35(4):311-318
pubmed: 32383458
Glycoconj J. 2021 Jun;38(3):331-340
pubmed: 33644826
Cell. 2010 Nov 24;143(5):737-49
pubmed: 21111234
Int J Mol Sci. 2022 Mar 28;23(7):
pubmed: 35409048
Protein Cell. 2020 Jun;11(6):401-416
pubmed: 32356279
Nature. 2009 Jul 9;460(7252):278-82
pubmed: 19506557
Mutat Res. 2007 Apr 1;617(1-2):33-45
pubmed: 17250856
PLoS One. 2010 Nov 29;5(11):e15062
pubmed: 21124777
Nat Rev Genet. 2020 Jan;21(1):44-62
pubmed: 31548659
Mutat Res Rev Mutat Res. 2019 Jan - Mar;779:1-35
pubmed: 31097147
Br J Cancer. 2014 Jun 10;110(12):2905-13
pubmed: 24853182
EMBO J. 2001 Feb 15;20(4):792-801
pubmed: 11179223
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Cell. 2001 May 18;105(4):445-57
pubmed: 11371342
Histopathology. 2012 Mar;60(4):586-96
pubmed: 22260438
Nat Commun. 2019 Mar 20;10(1):1289
pubmed: 30894531
Nature. 2018 Oct;562(7728):600-604
pubmed: 30323285
Curr Opin Cell Biol. 2021 Jun;70:91-99
pubmed: 33610905
Cell Cycle. 2015;14(19):3040-4
pubmed: 26266709
Science. 2005 Jan 7;307(5706):127-9
pubmed: 15637283
J Biol Chem. 2008 Apr 18;283(16):10930-8
pubmed: 18227068
Curr Biol. 2006 May 9;16(9):863-74
pubmed: 16682347
J Cell Biol. 2010 Jan 11;188(1):83-100
pubmed: 20065091
Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9228-9233
pubmed: 30150385
J Transl Med. 2013 Jun 10;11:142
pubmed: 23758705
Nat Protoc. 2007;2(5):1084-104
pubmed: 17546000
J Cell Biol. 2009 Jun 15;185(6):983-94
pubmed: 19528295
Trends Biochem Sci. 2021 Sep;46(9):718-730
pubmed: 33965314