Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (?) in pathogenic yeast Candida albicans.

Scientific reports

PubMedID: 28120914

Satpati S, Manohar K, Acharya N, Dixit A. Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (?) in pathogenic yeast Candida albicans. Sci Rep. 2017;741087.
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 (Pol?) is unique as it promotes efficient bypass of cyclobutane pyrimidine dimers. Interestingly, C. albicans is heterozygous in carrying two Pol? 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 Pol?. 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 p-p interactions spanning from thumb to PAD. This study suggests these ORFs as the homologues of yeast Pol?, and due to its heterogeneity in C. albicans they may play a significant role in pathogenicity.