Zebularine induces enzymatic DNA-protein crosslinks in 45S rDNA heterochromatin of Arabidopsis nuclei.
Arabidopsis
Arabidopsis Proteins
/ genetics
Cell Cycle Proteins
/ genetics
Cytidine
/ analogs & derivatives
DNA (Cytosine-5-)-Methyltransferases
/ genetics
DNA-Binding Proteins
/ genetics
Drug Resistance
Heterochromatin
/ drug effects
Membrane Transport Proteins
/ genetics
Mutagens
/ toxicity
Mutation
RNA, Ribosomal
/ drug effects
Transcription Factors
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
11 01 2022
11 01 2022
Historique:
accepted:
01
12
2021
received:
05
11
2021
pubmed:
15
12
2021
medline:
19
2
2022
entrez:
14
12
2021
Statut:
ppublish
Résumé
Loss of genome stability leads to reduced fitness, fertility and a high mutation rate. Therefore, the genome is guarded by the pathways monitoring its integrity and neutralizing DNA lesions. To analyze the mechanism of DNA damage induction by cytidine analog zebularine, we performed a forward-directed suppressor genetic screen in the background of Arabidopsis thaliana zebularine-hypersensitive structural maintenance of chromosomes 6b (smc6b) mutant. We show that smc6b hypersensitivity was suppressed by the mutations in EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 3 (ENT3), DNA METHYLTRANSFERASE 1 (MET1) and DECREASE IN DNA METHYLATION 1 (DDM1). Superior resistance of ent3 plants to zebularine indicated that ENT3 is likely necessary for the import of the drug to the cells. Identification of MET1 and DDM1 suggested that zebularine induces DNA damage by interference with the maintenance of CG DNA methylation. The same holds for structurally similar compounds 5-azacytidine and 2-deoxy-5-azacytidine. Based on our genetic and biochemical data, we propose that zebularine induces enzymatic DNA-protein crosslinks (DPCs) of MET1 and zebularine-containing DNA in Arabidopsis, which was confirmed by native chromatin immunoprecipitation experiments. Moreover, zebularine-induced DPCs accumulate preferentially in 45S rDNA chromocenters in a DDM1-dependent manner. These findings open a new avenue for studying genome stability and DPC repair in plants.
Identifiants
pubmed: 34904670
pii: 6460772
doi: 10.1093/nar/gkab1218
pmc: PMC8754632
doi:
Substances chimiques
AT4G05120 protein, Arabidopsis
0
Arabidopsis Proteins
0
Cell Cycle Proteins
0
DDM1 protein, Arabidopsis
0
DNA-Binding Proteins
0
Heterochromatin
0
Membrane Transport Proteins
0
Mutagens
0
RNA, Ribosomal
0
RNA, ribosomal, 45S
0
SMC6B protein, Arabidopsis
0
Transcription Factors
0
Cytidine
5CSZ8459RP
pyrimidin-2-one beta-ribofuranoside
7A9Y5SX0GY
MET1 protein, Arabidopsis
EC 2.1.1.-
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
244-258Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Plant Cell. 2010 Jan;22(1):34-47
pubmed: 20097869
Genome Biol. 2009;10(3):R25
pubmed: 19261174
Nat Rev Genet. 2014 Jun;15(6):394-408
pubmed: 24805120
Plant Cell. 2006 Feb;18(2):350-65
pubmed: 16399800
Mol Cell Biol. 2005 Jun;25(11):4727-41
pubmed: 15899874
Cancer Res. 1986 Nov;46(11):5511-7
pubmed: 2428479
DNA Repair (Amst). 2020 Mar;87:102787
pubmed: 31931324
Plant Cell. 2019 Jul;31(7):1579-1597
pubmed: 31036599
Mol Biol Evol. 2018 Jun 1;35(6):1547-1549
pubmed: 29722887
Chromosoma. 2004 Nov;113(5):258-69
pubmed: 15480725
J Biol Chem. 2003 Sep 12;278(37):35732-42
pubmed: 12810710
DNA Repair (Amst). 2004 Feb 3;3(2):155-61
pubmed: 14706349
Clin Chem. 2009 Apr;55(4):611-22
pubmed: 19246619
EMBO Rep. 2014 Apr;15(4):446-52
pubmed: 24562611
Clin Cancer Res. 2005 Jun 15;11(12):4571-9
pubmed: 15958643
Nat Cell Biol. 2021 Apr;23(4):391-400
pubmed: 33833428
Plant Reprod. 2013 Jun;26(2):65-81
pubmed: 23686220
Plant J. 2007 Apr;50(1):118-27
pubmed: 17346262
Plant Physiol. 2012 Jan;158(1):119-29
pubmed: 21994348
Anticancer Res. 2013 Aug;33(8):2989-96
pubmed: 23898051
PLoS One. 2010 Aug 24;5(8):e12388
pubmed: 20808780
Plant Cell. 2015 Jun;27(6):1788-800
pubmed: 26023162
Genes Cells. 2002 Oct;7(10):997-1007
pubmed: 12354094
Nat Genet. 1999 May;22(1):94-7
pubmed: 10319870
PLoS Biol. 2003 Dec;1(3):E67
pubmed: 14691539
Nat Plants. 2015 Sep 01;1:15127
pubmed: 27250680
Cell. 2012 Sep 28;151(1):167-80
pubmed: 23021223
Biochim Biophys Acta. 2007 May-Jun;1769(5-6):276-86
pubmed: 17341434
Cell. 2013 Mar 28;153(1):193-205
pubmed: 23540698
Cytogenet Genome Res. 2014;143(1-3):51-9
pubmed: 24685908
Nat Genet. 2003 May;34(1):65-9
pubmed: 12669067
Plant Cell. 2010 Sep;22(9):3118-29
pubmed: 20876829
Cell. 2014 Jul 17;158(2):327-338
pubmed: 24998930
Sci Rep. 2016 Jul 15;6:29657
pubmed: 27417498
Cell. 2013 Jan 17;152(1-2):352-64
pubmed: 23313553
Nat Rev Mol Cell Biol. 2017 Sep;18(9):563-573
pubmed: 28655905
Chromosome Res. 2000;8(6):527-41
pubmed: 11032322
Nucleosides Nucleotides Nucleic Acids. 2008 Feb;27(2):131-45
pubmed: 18205068
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Nature. 2009 Sep 17;461(7262):427-30
pubmed: 19734882
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
Genes Dev. 2001 Jul 15;15(14):1753-8
pubmed: 11459824
Plant Cell. 2019 Apr;31(4):775-790
pubmed: 30760561
Nucleic Acids Res. 2007;35(13):4301-12
pubmed: 17576694
Mol Cell. 2016 Nov 17;64(4):688-703
pubmed: 27871365
Plant J. 2007 Mar;49(5):855-64
pubmed: 17253988
Mutat Res. 1989 Jul;226(3):185-90
pubmed: 2473395
Cell. 2007 Sep 7;130(5):851-62
pubmed: 17803908
Plant J. 2020 Apr;102(1):68-84
pubmed: 31733119
Curr Biol. 2012 Oct 9;22(19):1825-30
pubmed: 22940470
Annu Rev Plant Biol. 2016 Apr 29;67:439-62
pubmed: 26653616
Front Plant Sci. 2017 May 24;8:866
pubmed: 28596780
Annu Rev Genet. 2013;47:1-32
pubmed: 23909437
Protoplasma. 2005 Oct;226(1-2):39-54
pubmed: 16231100
J Mol Biol. 1975 Nov 5;98(3):503-17
pubmed: 1195397
Mol Cell Biol. 2008 Jan;28(2):752-71
pubmed: 17991895
Genetics. 1999 Feb;151(2):831-8
pubmed: 9927473
Biochem Pharmacol. 2005 Jul 1;70(1):121-33
pubmed: 15885659
Plant Physiol. 2021 Apr 23;185(4):2003-2021
pubmed: 33566101
Plant J. 2009 Feb;57(3):542-54
pubmed: 18826433
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):632-7
pubmed: 10939915