DNA repair mechanisms in eukaryotes: Special focus in Entamoeba histolytica and related protozoan parasites

Hepatoprotective activity of Thymus vulgaris extract against Toxoplasma gondii infection

“…DNA damage can result in multiple lesions including mutations, insertions, deletions, translocations, and loss of chromosomes and essential genetic information. This genome instability may lead to apoptosis and fatal diseases [30]. It was demonstrated that T. gondii induced DNA damage in the liver cells agreeing with the other investigators who found that T. gondii induced DNA damage in the blood leukocytes, brain and retina [3,31,32].…”

DNA Repair in Pathogenic Eukaryotic Cells: Insights from Comparative Genomics of Parasitic Protozoan

“…The other key DNA repair mechanisms represented by BER, NER and MMR pathways operate to repair aberrant bases or nucleotides from a ssDNA using the complementary strand as template for DNA synthesis. As in E. histolytica [Lopez-Camarillo et al, 2009], the G. lamblia BER pathway appears to be largely incomplete, lacking apn1, mag1, ogg1, rad10, mus81 and mms4 genes. Both parasites live under oxygen-limiting conditions and have a highly reduced form of mitocondria called mitosomes [Tovar et al, 1999[Tovar et al, , 2003.…”

“…In order to identify amino acids sequences of E. histolytica, G. lamblia, P. falciparum and T. vaginalis proteins related to DNA repair factors, we performed similarity searches in the Eupath database (http://eupathdb.org/eupathdb/) using the Saccharomyces cerevisiae DNA repair proteins from HRR, NHEJ, BER, NER and MMR machineries as probes [reviewed in Lopez-Camarillo et al, 2009]. Putative gene products were selected from BLAST analysis against each parasite database using the Blosum 62 scoring matrix and the following criteria: (i) at least 20% identity and 35% homology to the query sequence and (ii) e-value lower than 0.002, unless a portion of the protein showed a very strong similarity.…”

Recombination and Diversification of the Variant Antigen Encoding Genes in the Malaria Parasite Plasmodium falciparum

“…By searching an organism's genome to identify genes encoding required components for the different repair pathways and by examining the products of repair, it is possible to infer how different evolutionary lineages have adapted their DNA repair pathways to suit their specific needs. For example, the DNA repair proteins Ku70/80 are thought to be required for C-NHEJ, but the genes encoding these proteins cannot be identified in the genomes of the protozoan parasites Trichomonas vaginalis and Encephalitozoon cuniculi, and only Ku70 is found in the gut parasite Entamoeba histolytica (62,6). Similarly, the kinetoplast parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania sp.…”

“…A well described example is the preference for which mechanism is utilized to repair DNA double-strand breaks (DSBs); higher eukaryotes show a pronounced propensity to use nonhomologous end joining (NHEJ) while the yeast Saccharomyces cerevisiae exhibits a strong preference for homologous recombination (HR), though both repair pathways are complete and present in these organisms (4). Recently it was discovered that some lineages of very divergent lower eukaryotes have lost components of DNA repair pathways (5,6,7,8), resulting in strong propensities toward certain types of DNA repair products and thus potentially influencing how these genomes change over time. Since DNA rearrangements play a crucial role in the diversification of important surface antigens, the availability and preferential use of different DNA repair pathways should be considered a key component of the process of antigenic variation.…”