Identification and in silico analysis of the origin recognition complex in the human fungal pathogen Candida albicans.

Abstract

DNA 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. Candida albicans, a major human fungal pathogen, is a diploid budding yeast that belongs to Ascomycota. However, C. albicans is significantly diverged from a well-studied model organism Saccharomyces cerevisiae, another ascomycete. The components of the DNA replication machinery in C. albicans remain 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 in C. albicans and determined their relatedness with those of other eukaryotes including several yeast species. Our extensive in silico studies demonstrate that the domain architecture of CaORC proteins share similarities with the ORC proteins of S. cerevisiae. We dissect the domain organization of ORC (trans-acting factors) subunits that seem to associate with DNA replication origins in C. albicans. We present a model of the 3D structure of CaORC4 to gain further insights of this protein’s function.