4.7 Article

The Role of DNA Topoisomerase Binding Protein 1 (TopBP1) in Genome Stability in Arabidopsis

Journal

PLANTS-BASEL
Volume 10, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/plants10122568

Keywords

TopBP1; topoisomerase II; DSBs; anaphase bridges; mitosis; meiosis

Categories

Funding

  1. BBSRC [BB/F02391X/1, BB/S00467X/1] Funding Source: UKRI

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The study reveals the important roles of TopBP1 in DNA repair, mitosis, and meiosis, as well as the functional interaction between TOPII and TopBP1. Mutant seedlings of Arabidopsis thaliana lacking TopBP1 show hypersensitivity to cisplatin and etoposide, suggesting a link between the functional interaction of TOPII and TopBP1 and this hypersensitivity. Inhibition of TOPII leads to the appearance of anaphase bridges at S phase/G2 stage during meiosis, highlighting the potential involvement of catenanes in this process.
DNA topoisomerase II (TOPII) plays a very important role in DNA topology and in different biological processes such as DNA replication, transcription, repair, and chromosome condensation in higher eukaryotes. TOPII has been found to interact directly with a protein called topoisomerase II binding protein 1 (TopBP1) which also seems to have important roles in DNA replication and repair. In this study, we conducted different experiments to assess the roles of TopBP1 in DNA repair, mitosis, and meiosis, exploring the relationship between TOPII activity and TopBP1. We found that topbp1 mutant seedlings of Arabidopsis thaliana were hypersensitive to cisplatin treatment and the inhibition of TOPII with etoposide produced similar hypersensitivity levels. Furthermore, we recognised that there were no significant differences between the WT and topbp1 seedlings treated with cisplatin and etoposide together, suggesting that the hypersensitivity to cisplatin in the topbp1 mutant could be related to the functional interaction between TOPII and TopBP1. Somatic and meiotic anaphase bridges appeared in the topbp1 mutant at similar frequencies to those when TOPII was inhibited with merbarone, etoposide, or ICFR-187. The effects on meiosis of TOPII inhibition were produced at S phase/G2 stage, suggesting that catenanes could be produced at the onset of meiosis. Thus, if the processing of the catenanes is impaired, some anaphase bridges can be formed. Also, the appearance of anaphase bridges at first and second division is discussed.

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