1. HandmanE (2001) Leishmaniasis: current status of vaccine development. Clin Microbiol Rev 14: 229–243.
2. MurrayHW, BermanJD, DaviesCR, SaraviaNG (2005) Advances in leishmaniasis. Lancet 366: 1561–1577.
3. LiraR, SundarS, MakhariaA, KenneyR, GamA, et al. (1999) Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani. J Infect Dis 180: 564–567.
4. SundarS, MoreDK, SinghMK, SinghVP, SharmaS, et al. (2000) Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31: 1104–1107.
5. HadighiR, MohebaliM, BoucherP, HajjaranH, KhamesipourA, et al. (2006) Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due to drug-resistant Leishmania tropica parasites. PLoS Med 3: e162.
6. RojasR, ValderramaL, ValderramaM, VaronaMX, OuelletteM, et al. (2006) Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. J Infect Dis 193: 1375–1383.
7. TorresDC, AdauiV, Ribeiro-AlvesM, RomeroGA, ArevaloJ, et al. (2010) Targeted gene expression profiling in Leishmania braziliensis and Leishmania guyanensis parasites isolated from Brazilian patients with different antimonial treatment outcomes. Infect Genet Evol 10: 727–733.
8. CampbellDA, ThomasS, SturmNR (2003) Transcription in kinetoplastid protozoa: why be normal? Microbes Infect 5: 1231–1240.
9. HaileS, PapadopoulouB (2007) Developmental regulation of gene expression in trypanosomatid parasitic protozoa. Curr Opin Microbiol 10: 569–577.
10. Martinez-CalvilloS, Vizuet-de-RuedaJC, Florencio-MartinezLE, Manning-CelaRG, Figueroa-AnguloEE (2010) Gene expression in trypanosomatid parasites. J Biomed Biotechnol 2010: 525241.
11. BeverleySM (1991) Gene amplification in Leishmania. Annu Rev Microbiol 45: 417–444.
12. BorstP, OuelletteM (1995) New mechanisms of drug resistance in parasitic protozoa. Annu Rev Microbiol 49: 427–460.
13. GrondinK, KundigC, RoyG, OuelletteM (1998) Linear amplicons as precursors of amplified circles in methotrexate-resistant Leishmania tarentolae. Nucleic Acids Res 26: 3372–3378.
14. UbedaJM, LegareD, RaymondF, OuameurAA, BoisvertS, et al. (2008) Modulation of gene expression in drug resistant Leishmania is associated with gene amplification, gene deletion and chromosome aneuploidy. Genome Biol 9: R115.
15. LeprohonP, LegareD, RaymondF, MadoreE, HardimanG, et al. (2009) Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic Acids Res 37: 1387–1399.
16. DowningT, ImamuraH, DecuypereS, ClarkTG, CoombsGH, et al. (2011) Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome Res 21: 2143–2156.
17. OuelletteM, HettemaE, WustD, Fase-FowlerF, BorstP (1991) Direct and inverted DNA repeats associated with P-glycoprotein gene amplification in drug resistant Leishmania. EMBO J 10: 1009–1016.
18. GrondinK, RoyG, OuelletteM (1996) Formation of extrachromosomal circular amplicons with direct or inverted duplications in drug-resistant Leishmania tarentolae. Mol Cell Biol 16: 3587–3595.
19. UbedaJM, RaymondF, MukherjeeA, PlourdeM, GingrasH, et al. (2014) Genome-wide stochastic adaptive DNA amplification at direct and inverted DNA repeats in the parasite leishmania. PLoS Biol 12: e1001868.
20. HaimeurA, BrochuC, GenestP, PapadopoulouB, OuelletteM (2000) Amplification of the ABC transporter gene PGPA and increased trypanothione levels in potassium antimonyl tartrate (SbIII) resistant Leishmania tarentolae. Mol Biochem Parasitol 108: 131–135.
21. CoderreJA, BeverleySM, SchimkeRT, SantiDV (1983) Overproduction of a bifunctional thymidylate synthetase-dihydrofolate reductase and DNA amplification in methotrexate-resistant Leishmania tropica. Proc Natl Acad Sci U S A 80: 2132–2136.
22. BeverleySM, CoderreJA, SantiDV, SchimkeRT (1984) Unstable DNA amplifications in methotrexate-resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization. Cell 38: 431–439.
23. KundigC, LeblancE, PapadopoulouB, OuelletteM (1999) Role of the locus and of the resistance gene on gene amplification frequency in methotrexate resistant Leishmania tarentolae. Nucleic Acids Res 27: 3653–3659.
24. BelloAR, NareB, FreedmanD, HardyL, BeverleySM (1994) PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major. Proc Natl Acad Sci U S A 91: 11442–11446.
25. WangJ, LeblancE, ChangCF, PapadopoulouB, BrayT, et al. (1997) Pterin and folate reduction by the Leishmania tarentolae H locus short-chain dehydrogenase/reductase PTR1. Arch Biochem Biophys 342: 197–202.
26. HightowerRC, Ruiz-PerezLM, WongML, SantiDV (1988) Extrachromosomal elements in the lower eukaryote Leishmania. J Biol Chem 263: 16970–16976.
27. WhiteTC, Fase-FowlerF, van LuenenH, CalafatJ, BorstP (1988) The H circles of Leishmania tarentolae are a unique amplifiable system of oligomeric DNAs associated with drug resistance. J Biol Chem 263: 16977–16983.
28. PapadopoulouB, RoyG, OuelletteM (1993) Frequent amplification of a short chain dehydrogenase gene as part of circular and linear amplicons in methotrexate resistant Leishmania. Nucleic Acids Res 21: 4305–4312.
29. ChiqueroMJ, OlmoA, NavarroP, Ruiz-PerezLM, CastanysS, et al. (1994) Amplification of the H locus in Leishmania infantum. Biochim Biophys Acta 1227: 188–194.
30. ButlerDK, YasudaLE, YaoMC (1995) An intramolecular recombination mechanism for the formation of the rRNA gene palindrome of Tetrahymena thermophila. Mol Cell Biol 15: 7117–7126.
31. OkunoY, HahnPJ, GilbertDM (2004) Structure of a palindromic amplicon junction implicates microhomology-mediated end joining as a mechanism of sister chromatid fusion during gene amplification. Nucleic Acids Res 32: 749–756.
32. VanHulleK, LemoineFJ, NarayananV, DowningB, HullK, et al. (2007) Inverted DNA repeats channel repair of distant double-strand breaks into chromatid fusions and chromosomal rearrangements. Mol Cell Biol 27: 2601–2614.
33. RosenbergSM, SheeC, FrischRL, HastingsPJ (2012) Stress-induced mutation via DNA breaks in Escherichia coli: a molecular mechanism with implications for evolution and medicine. Bioessays 34: 885–892.
34. LinCT, LinWH, LyuYL, Whang-PengJ (2001) Inverted repeats as genetic elements for promoting DNA inverted duplication: implications in gene amplification. Nucleic Acids Res 29: 3529–3538.
35. RattrayAJ, McGillCB, ShaferBK, StrathernJN (2001) Fidelity of mitotic double-strand-break repair in Saccharomyces cerevisiae: a role for SAE2/COM1. Genetics 158: 109–122.
36. TanakaH, YaoMC (2009) Palindromic gene amplification–an evolutionarily conserved role for DNA inverted repeats in the genome. Nat Rev Cancer 9: 216–224.
37. AssenmacherN, HopfnerKP (2004) MRE11/RAD50/NBS1: complex activities. Chromosoma 113: 157–166.
38. StrackerTH, PetriniJH (2011) The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 12: 90–103.
39. ShibataA, MoianiD, ArvaiAS, PerryJ, HardingSM, et al. (2014) DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol Cell 53: 7–18.
40. MimitouEP, SymingtonLS (2011) DNA end resection—unraveling the tail. DNA Repair (Amst) 10: 344–348.
41. GenoisMM, PaquetER, LaffitteMC, MaityR, RodrigueA, et al. (2014) DNA repair pathways in trypanosomatids: from DNA repair to drug resistance. Microbiol Mol Biol Rev 78: 40–73.
42. PaullTT, GellertM (2000) A mechanistic basis for Mre11-directed DNA joining at microhomologies. Proc Natl Acad Sci U S A 97: 6409–6414.
43. StewartGS, MaserRS, StankovicT, BressanDA, KaplanMI, et al. (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99: 577–587.
44. DolganovGM, MaserRS, NovikovA, TostoL, ChongS, et al. (1996) Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair. Mol Cell Biol 16: 4832–4841.
45. BressanDA, OlivaresHA, NelmsBE, PetriniJH (1998) Alteration of N-terminal phosphoesterase signature motifs inactivates Saccharomyces cerevisiae Mre11. Genetics 150: 591–600.
46. StraussB, WahlR (1964) The presence of breaks in the deoxyribonucleic acid of Bacillus subtilis treated in vivo with the alkylating agent, methylmethanesulfonate. Biochimica et Biophysica Acta (BBA)-Specialized Section on Nucleic Acids and Related Subjects 80: 116–126.
47. NareB, LubaJ, HardyLW, BeverleyS (1997) New approaches to Leishmania chemotherapy: pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity. Parasitology 114 Suppl: S101–110.
48. OuelletteM, DrummelsmithJ, El-FadiliA, KundigC, RichardD, et al. (2002) Pterin transport and metabolism in Leishmania and related trypanosomatid parasites. Int J Parasitol 32: 385–398.
49. McCullochR, BarryJD (1999) A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation. Genes Dev 13: 2875–2888.
50. GenoisMM, MukherjeeA, UbedaJM, BuissonR, PaquetE, et al. (2012) Interactions between BRCA2 and RAD51 for promoting homologous recombination in Leishmania infantum. Nucleic Acids Res 40: 6570–6584.
51. WenQ, ScorahJ, PhearG, RodgersG, RodgersS, et al. (2008) A mutant allele of MRE11 found in mismatch repair-deficient tumor cells suppresses the cellular response to DNA replication fork stress in a dominant negative manner. Mol Biol Cell 19: 1693–1705.
52. LeeJH, GhirlandoR, BhaskaraV, HoffmeyerMR, GuJ, et al. (2003) Regulation of Mre11/Rad50 by Nbs1: effects on nucleotide-dependent DNA binding and association with ataxia-telangiectasia-like disorder mutant complexes. J Biol Chem 278: 45171–45181.
53. YuZ, VogelG, CoulombeY, DubeauD, SpehalskiE, et al. (2012) The MRE11 GAR motif regulates DNA double-strand break processing and ATR activation. Cell Res 22: 305–320.
54. RobinsonNP, McCullochR, ConwayC, BrowittA, BarryJD (2002) Inactivation of Mre11 does not affect VSG gene duplication mediated by homologous recombination in Trypanosoma brucei. J Biol Chem 277: 26185–26193.
55. TanKS, LealST, CrossGA (2002) Trypanosoma brucei MRE11 is non-essential but influences growth, homologous recombination and DNA double-strand break repair. Mol Biochem Parasitol 125: 11–21.
56. HopfnerKP, KarcherA, CraigL, WooTT, CarneyJP, et al. (2001) Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell 105: 473–485.
57. OlsonE, NieveraCJ, LiuE, LeeAY, ChenL, et al. (2007) The Mre11 complex mediates the S-phase checkpoint through an interaction with replication protein A. Mol Cell Biol 27: 6053–6067.
58. LobachevKS, GordeninDA, ResnickMA (2002) The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements. Cell 108: 183–193.
59. ZhangY, SainiN, ShengZ, LobachevKS (2013) Genome-wide screen reveals replication pathway for quasi-palindrome fragility dependent on homologous recombination. PLoS Genet 9: e1003979.
60. ButlerDK, YasudaLE, YaoMC (1996) Induction of large DNA palindrome formation in yeast: implications for gene amplification and genome stability in eukaryotes. Cell 87: 1115–1122.
61. BrewerBJ, PayenC, RaghuramanMK, DunhamMJ (2011) Origin-dependent inverted-repeat amplification: a replication-based model for generating palindromic amplicons. PLoS Genet 7: e1002016.
62. LamarcheBJ, OrazioNI, WeitzmanMD (2010) The MRN complex in double-strand break repair and telomere maintenance. FEBS Lett 584: 3682–3695.
63. KroghBO, LlorenteB, LamA, SymingtonLS (2005) Mutations in Mre11 phosphoesterase motif I that impair Saccharomyces cerevisiae Mre11-Rad50-Xrs2 complex stability in addition to nuclease activity. Genetics 171: 1561–1570.
64. MaityR, PautyJ, KrietschJ, BuissonR, GenoisMM, et al. (2013) GST-His purification: a two-step affinity purification protocol yielding full-length purified proteins. J Vis Exp e50320.
65. DeryU, CoulombeY, RodrigueA, StasiakA, RichardS, et al. (2008) A glycine-arginine domain in control of the human MRE11 DNA repair protein. Mol Cell Biol 28: 3058–3069.
66. MoreiraW, LeblancE, OuelletteM (2009) The role of reduced pterins in resistance to reactive oxygen and nitrogen intermediates in the protozoan parasite Leishmania. Free Radic Biol Med 46: 367–375.
67. PapadopoulouB, RoyG, OuelletteM (1992) A novel antifolate resistance gene on the amplified H circle of Leishmania. EMBO J 11: 3601–3608.
68. El FadiliA, KundigC, OuelletteM (2002) Characterization of the folylpolyglutamate synthetase gene and polyglutamylation of folates in the protozoan parasite Leishmania. Mol Biochem Parasitol 124: 63–71.
69. SambrookJ, FritschEF, ManiatisT (1989) Molecular cloning: Cold spring harbor laboratory press New York.
70. DumasC, OuelletteM, TovarJ, CunninghamML, FairlambAH, et al. (1997) Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J 16: 2590–2598.