title: Transcriptomic response of yeast cells to ATX1 deletion under different copper levels.
abstract: Iron and copper homeostatic pathways are tightly linked since copper is required as a cofactor for high affinity iron transport. Atx1p plays an important role in the intracellular copper transport as a copper chaperone transferring copper from the transporters to Ccc2p for its subsequent insertion into Fet3p, which is required for high affinity iron transport.
  
  
  
  In this study, genome-wide transcriptional landscape of ATX1 deletants grown in media either lacking copper or having excess copper was investigated. ATX1 deletants were allowed to recover full respiratory capacity in the presence of excess copper in growth environment. The present study revealed that iron ion homeostasis was not significantly affected by the absence of ATX1 either at the transcriptional or metabolic levels, suggesting other possible roles for Atx1p in addition to its function as a chaperone in copper-dependent iron absorption. The analysis of the transcriptomic response of atx1∆/atx1∆ and its integration with the genetic interaction network highlighted for the first time, the possible role of ATX1 in cell cycle regulation, likewise its mammalian counterpart ATOX1, which was reported to play an important role in the copper-stimulated proliferation of non-small lung cancer cells.
  
  
  
  The present finding revealed the dispensability of Atx1p for the transfer of copper ions to Ccc2p and highlighted its possible role in the cell cycle regulation. The results also showed the potential of Saccharomyces cerevisiae as a model organism in studying the capacity of ATOX1 as a therapeutic target for lung cancer therapy.
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Bogazici University, 34342, Istanbul, Turkey. ayca.cankorur@boun.edu.tr.|Present address: Cambridge Systems Biology Centre & Department of Biochemistry, University of Cambridge, CB2 1GA, Cambridge, United Kingdom. ayca.cankorur@boun.edu.tr.
authors.forename: Ayca
authors.initials: A
authors.lastname: Cankorur-Cetinkaya
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Bogazici University, 34342, Istanbul, Turkey.|Present address: Diagnostic Centre for Genetic Diseases, Koc University Hospital, Davutpasa Cd. No:43010 Topkapı, Istanbul, Turkey.
authors.forename: Serpil
authors.initials: S
authors.lastname: Eraslan
authors.affiliation: Department of Chemical Engineering, Faculty of Engineering, Bogazici University, 34342, Istanbul, Turkey.
authors.forename: Betul
authors.initials: B
authors.lastname: Kirdar
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D003300:Copper / Q000378:metabolism*; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; D003300:Copper
keywords: Cell cycle regulation; Copper chaperon; Copper homeostasis; Copper transport; Menkes disease; Wilson disease; Yeast