title: DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.
abstract: Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen.
authors.affiliation: Department of Microbiology and Immunology, Columbia University, New York, New York, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Columbia University, New York, New York, USA.
authors.forename: Lorraine S
authors.initials: LS
authors.lastname: Symington
authors.affiliation: Department of Microbiology and Immunology, Columbia University, New York, New York, USA Division of Infectious Diseases, Department of Medicine, Columbia University, New York, New York, USA df2260@columbia.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D016054:DNA, Protozoan / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance; D019143:Evolution, Molecular; D018503:Genome, Protozoan; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan