Characterization of uracil-DNA glycosylase activity from Trypanosoma cruzi and its stimulation by AP endonuclease

Fárez-Vidal, María Esther; Gallego, Cláribel; Ruíz-Pérez, Luis M.; González-Pacanowska, Dolores

doi:10.1093/nar/29.7.1549

Cited by 23 publications

(24 citation statements)

References 43 publications

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“…Using a specific ethidium bromide fluorescence assay, recombinant T. cruzi uracil DNA glycosylase (TcUNG) was shown to specifically excise uracil from DNA. In addition, the activity was stimulated in the presence of AP endonuclease (44), similar to what was observed with the human enzymes (45). Moreover, a functional role for the enzyme was confirmed, since the expression of TcUNG in an E. coli ung mutant restored the WT phenotype (46).…”

Section: Dna Glycosylases and Ap Endonucleasessupporting

confidence: 73%

DNA Repair Pathways in Trypanosomatids: from DNA Repair to Drug Resistance

Genois

Paquet

Laffitte

et al. 2014

Microbiol Mol Biol Rev

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SUMMARY All living organisms are continuously faced with endogenous or exogenous stress conditions affecting genome stability. DNA repair pathways act as a defense mechanism, which is essential to maintain DNA integrity. There is much to learn about the regulation and functions of these mechanisms, not only in human cells but also equally in divergent organisms. In trypanosomatids, DNA repair pathways protect the genome against mutations but also act as an adaptive mechanism to promote drug resistance. In this review, we scrutinize the molecular mechanisms and DNA repair pathways which are conserved in trypanosomatids. The recent advances made by the genome consortiums reveal the complete genomic sequences of several pathogens. Therefore, using bioinformatics and genomic sequences, we analyze the conservation of DNA repair proteins and their key protein motifs in trypanosomatids. We thus present a comprehensive view of DNA repair processes in trypanosomatids at the crossroads of DNA repair and drug resistance.

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Section: Dna Glycosylases and Ap Endonucleasessupporting

confidence: 73%

DNA Repair Pathways in Trypanosomatids: from DNA Repair to Drug Resistance

Genois

Paquet

Laffitte

et al. 2014

Microbiol Mol Biol Rev

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“…UvsX recombinase and Dda helicase are reported to rescue stalled T4 replication forks in vitro (29). Finally, ORF173 encodes a homologue of uracil-DNA glycosylases that removes uracil in DNA that can arise either by misincorporation of dUTP during DNA synthesis or by the spontaneous deamination of cytosine (22). Nucleotide metabolism.…”

Section: Resultsmentioning

confidence: 99%

Ma-LMM01 Infecting Toxic Microcystis aeruginosa Illuminates Diverse Cyanophage Genome Strategies

et al. 2008

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Cyanobacteria and their phages are significant microbial components of the freshwater and marine environments. We identified a lytic phage, Ma-LMM01, infecting Microcystis aeruginosa, a cyanobacterium that forms toxic blooms on the surfaces of freshwater lakes. Here, we describe the first sequenced freshwater cyanomyovirus genome of Ma-LMM01. The linear, circularly permuted, and terminally redundant genome has 162,109 bp and contains 184 predicted protein-coding genes and two tRNA genes. The genome exhibits no colinearity with previously sequenced genomes of cyanomyoviruses or other Myoviridae. The majority of the predicted genes have no detectable homologues in the databases. These findings indicate that Ma-LMM01 is a member of a new lineage of the Myoviridae family. The genome lacks homologues for the photosynthetic genes that are prevalent in marine cyanophages. However, it has a homologue of nblA, which is essential for the degradation of the major cyanobacteria light-harvesting complex, the phycobilisomes. The genome codes for a site-specific recombinase and two prophage antirepressors, suggesting that it has the capacity to integrate into the host genome. Ma-LMM01 possesses six genes, including three coding for transposases, that are highly similar to homologues found in cyanobacteria, suggesting that recent gene transfers have occurred between Ma-LMM01 and its host. We propose that the Ma-LMM01 NblA homologue possibly reduces the absorption of excess light energy and confers benefits to the phage living in surface waters. This phage genome study suggests that light is central in the phage-cyanobacterium relationships where the viruses use diverse genetic strategies to control their host's photosynthesis.The cyanobacterium Microcystis aeruginosa is a toxic, bloomforming bacteria found in eutrophic freshwaters throughout the world (12). The bacterium produces potent hepatotoxins, cyclic peptides called "microcystins," which inhibit eukaryotic protein phosphatase types 1 and 2A and can cause hepatocellular carcinoma (42,53,82). Blooms of M. aeruginosa can lead to the deaths of livestock and humans and pose serious problems for water management (12, 13).The mechanisms controlling bloom initiation and termination remain unclear; however, there have been many studies concerning the effects of environmental factors on M. aeruginosa growth (57). Recently, viral mortality of algae was recognized as one of the factors involved in the termination of algal blooms, including M. aeruginosa blooms (10,52,71,74,75). We previously reported culturing the lytic cyanophage Ma-LMM01 infecting the toxic M. aeruginosa strain NIES298 (81). Currently, M. aeruginosa NIES298 and Ma-LMM01 are the sole culture host/virus system to study interactions between a toxic cyanobacterium and its phage.Ma-LMM01 is a member of the Myoviridae family with a contractile tail (81), the distinctive morphological feature of this viral family. Myoviridae has at least six subgroups: T4-, P1-, P2-, Mu-, SPO1-, and H-like phages (23). These subgroups sh...

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“…To date, several BER enzymes, such as uracil-DNA-glycosylase, 49 polβ, 50 and a class II AP endonuclease, 23 have been identified in parasites. Here and in a previous study, we have shown that the class II AP-endonuclease of L. major (LMAP) is able to confer resistance against alkylation damage in different E. coli DNA repair-deficient backgrounds.…”

Section: Discussionmentioning

confidence: 99%

“…26,44,45 LMAP thus maintains a generic positive charge layout that could accommodate non-sequence specific DNA features and a sufficiently rigid catalytic surface to function only when the appropriate substrate is presented. It has been shown that DNA glycosylases shield the site of damage until they are displaced by an AP endonuclease [46][47][48][49] and it is possible that accessory features on the surface of LMAP facilitate interactions that enable access to a glycosylaseprotected AP-site. LMAP has very little relative surface electrostatic potential away from the catalytic site but could interact with other proteins, through hydrophobic interactions or complementation of localized weakly positive potential.…”

Section: Kinetic Analysis Of the Lmap Dna Repair Activitiesmentioning

confidence: 99%