Correction: Identification of Plasmodium falciparum DNA Repair Protein Mre11 with an Evolutionarily Conserved Nuclease Function.

[This corrects the article DOI: 10.1371/journal.pone.0125358.].

UvrA and UvrC subunits of the Mycobacterium tuberculosis UvrABC excinuclease interact independently of UvrB and DNA.

The UvrABC excinuclease plays a vital role in bacterial nucleotide excision repair. While UvrA and UvrB subunits associate to form a UvrA2 B2 complex, interaction between UvrA and UvrC has not been demonstrated or quantified in any bacterial species. Here, using Mycobacterium tuberculosis UvrA (MtUvrA), UvrB (MtUvrB) and UvrC (MtUvrC) subunits, we show that MtUvrA binds to MtUvrB and equally well to MtUvrC with submicromolar affinity. Furthermore, MtUvrA forms a complex with MtUvrC both in vivo and in vitro, independently of DNA and UvrB. Collectively, these findings reveal new insights into the pairwise relationships between the subunits of the UvrABC incision complex.

Identification of Plasmodium falciparum DNA Repair Protein Mre11 with an Evolutionarily Conserved Nuclease Function.

The eukaryotic Meiotic Recombination protein 11 (Mre11) plays pivotal roles in the DNA damage response (DDR). Specifically, Mre11 senses and signals DNA double strand breaks (DSB) and facilitates their repair through effector proteins belonging to either homologous recombination (HR) or non-homologous end joining (NHEJ) repair mechanisms. In the human malaria parasite Plasmodium falciparum, HR and alternative-NHEJ have been identified; however, little is known about the upstream factors involved in the DDR of this organism. In this report, we identify a putative ortholog of Mre11 in P. falciparum (PfalMre11) that shares 22% sequence similarity to human Mre11. Homology modeling reveals striking structural resemblance of the predicted PfalMre11 nuclease domain to the nuclease domain of Saccharomyces cerevisiae Mre11 (ScMre11). Complementation analyses reveal functional conservation of PfalMre11 nuclease activity as demonstrated by the ability of the PfalMre11 nuclease domain, in conjunction with the C-terminal domain of ScMre11, to functionally complement an mre11 deficient yeast strain. Functional complementation was virtually abrogated by an amino acid substitution in the PfalMre11 nuclease domain (D398N). PfalMre11 is abundant in the mitotically active trophozoite and schizont stages of P. falciparum and is up-regulated in response to DNA damage, suggesting a role in the DDR. PfalMre11 exhibits physical interaction with PfalRad50. In addition, yeast 2-hybrid studies show that PfalMre11 interacts with ScRad50 and ScXrs2, two important components of the well characterized Mre11-Rad50-Xrs2 complex which is involved in DDR signaling and repair in S. cerevisiae, further supporting a role for PfalMre11 in the DDR. Taken together, these findings provide evidence that PfalMre11 is an evolutionarily conserved component of the DDR in Plasmodium.