Interestingly, 42 of a total of genes 328 genes analyzed (13%) ar

Interestingly, 42 of a total of genes 328 genes analyzed (13%) are underrepresented in the human genome (E-value > 10−30). These genes constitute 16 groups HIF activation of orthologs, and only one group could

be assigned to the SF1 (LmjF.09.0590, Tb11.01.4440, and Tc00.1047053509029.120), the other 15 groups belong to the ‘unclassified’ category (for details see: Data S2). These helicases, probably absent in humans could be interesting as therapeutic targets. Kinetoplast DNA is mitochondrial DNA of trypanosomatid organisms, and this DNA is in the form of a network of thousands of topological interlocked DNA circles, which is a structure unique in nature (Ryan et al., 1988). Each parasite cell contains

only one network conformed by mini-circles and maxi-circles, which replication and maintenance involves specific helicases. RNA editing in the mitochondrion of kinetoplastid protozoa results in the post-transcriptional addition and deletion of uridine residues in mRNAs. Editing of mRNAs, where different helicases participate, can lead to the formation of initiation codons for mitochondrial translation, the correction of frame-shifted genes at the RNA level, and in extensively edited mRNAs, the formation of complete reading frames (Hajduk & Ochsenreiter, 2010). In 1993, a new base, β-d-glucopyranosyloxymethyluracil (base J), was identified in the nuclear DNA of T. brucei. Base J is PI3K inhibitor the first hyper-modified base found in eukaryotic DNA. It is present in all kinetoplastid flagellates analyzed and some unicellular flagellates closely related to Trypanosomatids, but it has not been found in other protozoa or in metazoa. Interestingly, the C-terminal half of the putative ‘De Novo J Synthesis Factor’ (JBP2, Tb927.7.4650) is homologous to the Swi2/Snf2 family of ATPase DNA helicase proteins involved in chromatin remodeling (Borst & Sabatini, 2008). Finally, mRNA maturation in trypanosomes differs from the process in most

eukaryotes mainly because protein-coding genes are transcribed into polycistronic RNAs in this organism. Monocistronic mRNAs are processed from polycistronic precursors by trans-splicing Farnesyltransferase of a capped spliced leader to the 5′ end and simultaneous 3′ polyadenylation of the upstream mRNA. Multiple helicases participate in distinct splicing steps to unwind transient interactions during spliceosome assembly (Liang et al., 2003). Helicases have been proposed as promising drug targets for cancer (Gupta & Brosh, 2008), viral infections therapies (Kwong et al., 2005), and also for parasitic diseases such as Malaria (Tuteja, 2007). In the specific case of Kinetoplastids, the presence of unique structures and biological processes involving specific helicases points out these superfamily of proteins as potential anti-parasitic drug targets.

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