Number of the records: 1
Zebularine induces enzymatic DNA-protein crosslinks in 45S rDNA heterochromatin of Arabidopsis nuclei
- 1.
SYSNO ASEP 0556429 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Zebularine induces enzymatic DNA-protein crosslinks in 45S rDNA heterochromatin of Arabidopsis nuclei Author(s) Procházková, Klára (UEB-Q) ORCID
Finke, A. (DE)
Tomaštíková, Eva (UEB-Q) RID, ORCID
Filo, Jaroslav (UEB-Q)
Bente, H. (DE)
Dvořák, P. (CZ)
Ovečka, M. (CZ)
Šamaj, J. (CZ)
Pečinka, Aleš (UEB-Q) ORCID, RIDNumber of authors 9 Source Title Nucleic Acids Research. - : Oxford University Press - ISSN 0305-1048
Roč. 50, č. 1 (2022), s. 244-258Number of pages 15 s. Language eng - English Country GB - United Kingdom Keywords CYTIDINE ANALOG ZEBULARINE ; METHYLATION INHIBITOR ; DAMAGE REPAIR OECD category Cell biology R&D Projects GA19-13848S GA ČR - Czech Science Foundation (CSF) EF16_019/0000827 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEB-Q - RVO:61389030 UT WOS 000749588900022 EID SCOPUS 85124777747 DOI 10.1093/nar/gkab1218 Annotation 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. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2023 Electronic address http://doi.org/10.1093/nar/gkab1218
Number of the records: 1