title: Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans.
abstract: Genomic instability in Candida albicans is believed to play a crucial role in fungal pathogenesis. DNA polymerases contribute significantly to stability of any genome. Although Candida Genome database predicts presence of S. cerevisiae DNA polymerase orthologs; functional and structural characterizations of Candida DNA polymerases are still unexplored. DNA polymerase eta (Polη) is unique as it promotes efficient bypass of cyclobutane pyrimidine dimers. Interestingly, C. albicans is heterozygous in carrying two Polη genes and the nucleotide substitutions were found only in the ORFs. As allelic differences often result in functional differences of the encoded proteins, comparative analyses of structural models and molecular dynamic simulations were performed to characterize these orthologs of DNA Polη. Overall structures of both the ORFs remain conserved except subtle differences in the palm and PAD domains. The complementation analysis showed that both the ORFs equally suppressed UV sensitivity of yeast rad30 deletion strain. Our study has predicted two novel molecular interactions, a highly conserved molecular tetrad of salt bridges and a series of π-π interactions spanning from thumb to PAD. This study suggests these ORFs as the homologues of yeast Polη, and due to its heterogeneity in C. albicans they may play a significant role in pathogenicity.
authors.affiliation: Department of translational research and technology development, Computational Biology and Bioinformatics laboratory, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Satpati
authors.affiliation: Department of Infectious Disease Biology, Laboratory of Genomic instability and Diseases, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India.
authors.forename: Kodavati
authors.initials: K
authors.lastname: Manohar
authors.affiliation: Department of Infectious Disease Biology, Laboratory of Genomic instability and Diseases, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India.
authors.forename: Narottam
authors.initials: N
authors.lastname: Acharya
authors.affiliation: Department of translational research and technology development, Computational Biology and Bioinformatics laboratory, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India.
authors.forename: Anshuman
authors.initials: A
authors.lastname: Dixit
mesh_terms: D000483:Alleles; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics; D005816:Genetic Complementation Test; D056004:Molecular Dynamics Simulation; D016366:Open Reading Frames; D025941:Protein Interaction Mapping; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases