Depletion of dimeric all-α dUTPase induces DNA strand breaks and impairs cell cycle progression in Trypanosoma brucei

Castillo-Acosta, Víctor M.; Estévez, Antonio M.; Vidal, Antonio E.; Pérez, Luis; González-Pacanowska, Dolores

doi:10.1016/j.biocel.2008.06.009

Cited by 39 publications

(55 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since in Trypanosoma [15], abnormally high levels of uracil in DNA induce a change in BER activities, we measured in vitro uracil excision (U∶G) and AP site (AP∶G) repair activities in protein extracts comparing WT to RNAi/ DUT1 plants, as described in [20], [21] (Figure 4A). We compared the repair kinetics of uracil versus apurinic site with the same amounts of protein extracted from either WT or RNAi/ DUT1 seedlings.…”

Section: Resultsmentioning

confidence: 99%

“…In C. elegans ( Caenorhabditis elegans ), partial loss of dUTPase activity results in the accumulation of RAD51 foci in the chromatin suggesting that DSBs have been created and are being repaired by HR [14]. Decrease of dUTPase activity in Trypanosoma ( Trypanosoma brucei ), also results in the introduction of DSBs, as chromosome fragmentation is observed [15]. Taking together these results, we hypothesized that knocking-down dUTPase expression would lead to an increase in DSB formation and thus could influence HR levels in Arabidopsis ( Arabidopsis thaliana ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Homologous Recombination Is Stimulated by a Decrease in dUTPase in Arabidopsis

et al. 2011

View full text Add to dashboard Cite

Deoxyuridine triphosphatase (dUTPase) enzyme is an essential enzyme that protects DNA against uracil incorporation. No organism can tolerate the absence of this activity. In this article, we show that dUTPase function is conserved between E. coli (Escherichia coli), yeast (Saccharomyces cerevisiae) and Arabidopsis (Arabidopsis thaliana) and that it is essential in Arabidopsis as in both micro-organisms. Using a RNA interference strategy, plant lines were generated with a diminished dUTPase activity as compared to the wild-type. These plants are sensitive to 5-fluoro-uracil. As an indication of DNA damage, inactivation of dUTPase results in the induction of AtRAD51 and AtPARP2, which are involved in DNA repair. Nevertheless, RNAi/DUT1 constructs are compatible with a rad51 mutation. Using a TUNEL assay, DNA damage was observed in the RNAi/DUT1 plants. Finally, plants carrying a homologous recombination (HR) exclusive substrate transformed with the RNAi/DUT1 construct exhibit a seven times increase in homologous recombination events. Increased HR was only detected in the plants that were the most sensitive to 5-fluoro-uracils, thus establishing a link between uracil incorporation in the genomic DNA and HR. Our results show for the first time that genetic instability provoked by the presence of uracils in the DNA is poorly tolerated and that this base misincorporation globally stimulates HR in plants.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Homologous Recombination Is Stimulated by a Decrease in dUTPase in Arabidopsis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…For annotation purposes, the genome has been opened to the small terminase gene (6). Seurat also encodes a dUTPase to ensure low levels of cellular dUTP through the hydrolysis of dUTP into dUMP and PP i (7). …”

Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequence of Enterotoxigenic Escherichia coli Siphophage Seurat

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Components for most of the common DNA repair pathways have been identified in trypanosomes and some have been characterized (Passos-Silva et al). Proteins homologous to certain elements of the mammalian mismatch repair pathway (Bell et al, 2004), base excision repair (Castillo-Acosta et al, 2008), nucleotide excision repair (Lee et al, 2007) and homologous recombination (Glover et al, 2008) are present. One aspect of DNA repair not yet described in trypanosomes involves removal of aberrant methyl groups; such reactions are catalyzed by methylated-DNA glycosylases, alkyl transferases, and oxidative demethylases in other systems (Sedgwick et al, 2007).…”

Section: Introductionmentioning

confidence: 99%