Abstract
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.
Highlights
Topological relationships within the DNA sequence and structure of an organism modulate almost every physiological function of the genome [1]
In order to assess if DNA repair was affected in the topbp1 mutant, different treatments were conducted to induce artificial double-strand break (DSB) and inhibit Topoisomerase II (TOPII)
After 16 days, topbp1 mutant seedlings were hypersensitive to cisplatin to a similar level when treated with both cisplatin and the TOPII inhibitor etoposide as compared to WT seedlings treated with cisplatin + etoposide
Summary
Topological relationships within the DNA sequence and structure of an organism modulate almost every physiological function of the genome [1]. The double-stranded DNA helix structure is required to allow the assembly of different multiprotein complexes during transcription and replication. Topoisomerases are enzymes involved in modulating the DNA topology that is essential for the different nuclear processes of the cell [2]. The importance of topoisomerases is present in all areas of the chromosome structure, from nucleosome assembly to chromosome segregation [3]. TOPII is involved in different DNA biological functions, such as chromosome condensation and chromosome segregation [6]. Most eukaryotic cells have only a single version of the TOPII enzyme, but mammalian cells express two TOPII isoforms (TOPIIα and TOPIIβ). TOPIIα is essential in all cell types for separating replicated chromosomes, whereas TOPIIβ is mostly required for normal cellular development during certain processes such as the regulation of transcription in some cell types [7]
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