By Patrick Forterre (auth.), Yves Pommier (eds.)
DNA topoisomerases signify a necessary relatives of DNA processing enzymes and a lot of topoisomerase inhibitors are used clinically for the remedy of assorted human cancers. Novels medicines are in scientific improvement either opposed to kind I and kind II topoisomerases. The booklet will contain simple biochemical and structural experiences for the cancer-relevant topoisomerases. it's going to describe how topoisomerase dysfunctions can harm the genome and raise the danger of cancers, and the involvement of topoisomerases in programmed mobilephone demise. The publication also will current many of the topoisomerase inhibitors in scientific use and improvement and their molecular and mobile mechanisms of action.
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Extra resources for DNA Topoisomerases and Cancer
Sample text
Although this enzyme has not yet been purified, genetic evidences now strongly support this hypothesis (Hartung et al. 2002; Hartung and Puchta 2001; Sugimoto-Shirasu et al. 2002, 2005; Yin et al. 2002). Mutations in any one of the two subunits of Topo VI from A. thaliana has a dramatic effect on plant growth and they produce a dwarf phenotype. This results from inhibition of chromosomal polyploidization, a process known as endoreduplication. Indeed, normal plant cells expend their size by multiplying the number of their chromosomes up to 32, and the size of the plant itself is directly linked to the size of the cells.
In agreement with this grouping, reverse gyrase cleaves, preferentially, DNA at sequences that are similar to those cleaved by E. coli protein Z (Kovalsky et al. 1990). Several hyperthermophilic archaea of the phylum Crenarchaea and bacteria of the order Aquificales contain two reverse gyrases that originated by gene duplication in these respective lineages (Brochier-Armanet and Forterre 2007). The transcription pattern of the two Sulfolobus solfataricus reverse gyrases indicates a functional differentiation of these two proteins, suggesting at least two different functional roles for reverse gyrase in vivo (Garnier and Nadal 2009).
Phylogenetic analysis has clearly shown that archaeal gyrases have been recruited from bacteria by lateral gene transfer (Forterre et al. 2007). Bacterial gyrase genes have been also transferred to plants, via the chloroplast route. The A. thaliana DNA gyrase subunits branch with those of cyanobacteria in phylogenetic analysis and can complement E. coli gyrase mutants (Forterre et al. 2007; Cho et al. 2004). Genetic analyses have shown that the DNA gyrase of A. thaliana is involved in the segregation of chloroplast DNA (Cho et al.