Identification andin silicoanalysis of the origin recognition complex in the human fungal pathogenCandida albicans

Abstract

AbstractDNA replication in eukaryotes is initiated by the orchestrated assembly and association of initiator proteins (heterohexameric Origin Recognition Complex, ORC) on the replication origins. These functionally conserved proteins play significant roles in diverse cellular processes besides their central role in ignition of DNA replication at origins. WhileCandida albicans, a major human fungal pathogen, is an ascomycetous, asexual, diploid budding yeast but it is significantly diverged from a much better studied model organismSaccharomyces cerevisiae. The components of the DNA replication machinery inC. albicansremain largely uncharacterized. Identification of factors required for DNA replication is essential for understanding the evolution of the DNA replication machinery. We identified the putative ORC homologs inC. albicansand determined their relatedness with those of other eukaryotes including several yeast species. Our extensivein silicostudies demonstrate that the domain architecture of CaORC proteins share similarities with the ORC proteins ofS. cerevisiae. We dissect the domain organization of ORC (trans-acting factors) proteins that seem to associate with DNA replication origins inC. albicans. We present a model of the 3D structure of CaORC4 to gain further insights of this protein’s function.