title: Role of a Candida albicans Nrm1/Whi5 homologue in cell cycle gene expression and DNA replication stress response.
abstract: To explore cell cycle regulation in the dimorphic fungus Candida albicans, we identified and characterized CaNrm1, a C. albicans homologue of the Saccharomyces cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian Rb, regulate the cell cycle transcription programme during the G1 phase. CaNRM1 is able to complement the phenotypes of both whi5 and nrm1 mutants in S. cerevisiae. In C. albicans, global transcription analysis of the CaNRM1 deletion mutant reveals a preferential induction of G1- and G1/S-specific genes. CaNrm1 interacts genetically with the C. albicans MBF functional homologue, and physically with its subunit CaSwi4. Similar to S. cerevisiae Whi5, CaNrm1 subcellular localization oscillates with the cell cycle between the nucleus and the cytoplasm. Deletion of CaNRM1 further results in increased resistance to hydroxyurea, an inhibitor of DNA replication; analysis of the expression of ribonucleotide reductase, the target of hydroxyurea, suggests that its transcriptional induction in response to hydroxyurea is regulated via CaNrm1, and biochemical analysis shows that hydroxyurea causes disruption of the interaction of CaNrm1 with CaSwi4. Furthermore, induction of the hyphal-specific genes is dampened under certain conditions in the Canrm1(-/-) mutant, suggesting that the cell cycle transcription programme can influence the morphogenetic transcription programme of C. albicans.
authors.affiliation: Department of Molecular Microbiology, Technion - IIT and the Rappaport Institute for Research in the Medical Sciences, Haifa 31096, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Ofir
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Esther
authors.initials: E
authors.lastname: Weindling
authors.forename: Tsvia
authors.initials: T
authors.lastname: Gildor
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Barker
authors.forename: P David
authors.initials: PD
authors.lastname: Rogers
authors.forename: Daniel
authors.initials: D
authors.lastname: Kornitzer
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development*; D002453:Cell Cycle; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004261:DNA Replication; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018816:Genes, cdc; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping; D012097:Repressor Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D005656:Fungal Proteins; C513403:Nrm1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C508130:Whi5 protein, S cerevisiae