Plasmodium falciparum origin recognition complex subunit 1 (PfOrc1) functionally complements Δsir3 mutant of Saccharomyces cerevisiae

• PfOrc1 is a functional homolog of Sir3 and possesses Sir3/Orc1 like silencing activity.
• PfOrc1 could complement yeast Sir3 activity during telomere silencing.
• Silencing function of PfOrc1 is dependent on Sir2.
• The amino-terminal domain of PfOrc1 harbors silencing activity similar to ScSir3.

Telomere position effect efficiently controls silencing of subtelomeric var genes, which are involved in antigenic variation in human malaria parasite Plasmodium falciparum. Although, PfOrc1 has been found to be associated with PfSir2 in the silencing complex, its function in telomere silencing remained uncertain especially due to an apparent lack of BAH domain at its amino-terminal region. Here we report that PfOrc1 possesses a Sir3/Orc1 like silencing activity. Using yeast as a surrogate organism we have shown that PfOrc1 could complement yeast Sir3 activity during telomere silencing in a Sir2 dependent manner. By constructing a series of chimera between PfOrc1 and ScSir3 we have observed that the amino-terminal domain of PfOrc1 harbors silencing activity similar to that present in the amino-terminal domain of ScSir3. We further generated several amino-terminal deletion mutants to dissect out such silencing activity and found that the first seventy amino acids at the amino-terminal domain are dispensable for its activity. Thus our results strongly supports that PfOrc1 may have a role in telomere silencing in this parasite. This finding will help to decipher the mechanism of telomere position effect in P. falciparum.

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