Malaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity.

TitleMalaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity.
Publication TypeJournal Article
Year of Publication2014
AuthorsKirkman L, Lawrence EA, Deitsch K
JournalNucleic Acids Res
Date Published2014 Jan
KeywordsBase Sequence, DNA Breaks, Double-Stranded, DNA End-Joining Repair, Gene Conversion, Genome, Protozoan, Molecular Sequence Data, Plasmodium falciparum, Recombinational DNA Repair

Malaria parasites replicate asexually within their mammalian hosts as haploid cells and are subject to DNA damage from the immune response and chemotherapeutic agents that can significantly disrupt genomic integrity. Examination of the annotated genome of the parasite Plasmodium falciparum identified genes encoding core proteins required for the homologous recombination (HR) pathway for repairing DNA double-strand breaks (DSBs), but surprisingly none of the components of the canonical non-homologous end joining (C-NHEJ) pathway were identified. To better understand how malaria parasites repair DSBs and maintain genome integrity, we modified the yeast I-SceI endonuclease system to generate inducible, site-specific DSBs within the parasite's genome. Analysis of repaired genomic DNA showed that parasites possess both a typical HR pathway resulting in gene conversion events as well as an end joining (EJ) pathway for repair of DSBs when no homologous sequence is available. The products of EJ were limited in number and identical products were observed in multiple independent experiments. The repair junctions frequently contained short insertions also found in the surrounding sequences, suggesting the possibility of a templated repair process. We propose that an alternative end-joining pathway rather than C-NHEJ, serves as a primary method for repairing DSBs in malaria parasites.

Alternate JournalNucleic Acids Res.
PubMed ID24089143
PubMed Central IDPMC3874194
Grant ListAI 52390 / AI / NIAID NIH HHS / United States
AI 99327 / AI / NIAID NIH HHS / United States
AI76635 / AI / NIAID NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587