Fig. 6. Model for dynamic telomeric heterochromatin assembly and relocation during blood-stage development. (A) Hypothetical model of the differential spreading of P. falciparum telomeric proteins. Orc1 (green ovals) might bind directly to telomere and to TARE1-3 repeats via its N-terminal DNA-binding domain. The interaction of Orc1 with other unknown TARE6-binding molecules (adaptor proteins) might lead to telomere bending. Sir2 (red circles) might be recruited via interaction with an unknown telomere-associated protein (black curve) or alternatively with Orc1. Sir2 might then deacetylate telomeric histone tails (Merrick and Duraisingh, 2007), promoting heterochromatin formation and spreading towards the coding region. (B) Model for the dynamics of telomere chromatin factors during the P. falciparum blood-stage cycle. During ring stage (left), parasite telomeres form clusters at the nuclear periphery and associate with Sir2 (red circles) and Orc1 (green circles) (i). This period (G phase) is followed by multiple rounds of DNA synthesis and nuclear mitosis (trophozoite stage, middle), which produce a multinucleate schizont (right). Our data show that Orc1, Sir2 and telomeric clusters disassemble prior to DNA replication (ii). Telomeric components assemble in the newly formed nuclei (iii) and will be maintained for the next cycle. We speculate that the relocation events are driven by specific post-translational modifications. Alternatively, cytoplasmic Orc1 and Sir2 might correspond to newly synthesized proteins necessary to accommodate the demands of the rapid nuclear divisions occurring during S-M phase.