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Identification of intragenic mutations in the Hansenula polymorpha PEX6 gene that affect peroxisome biogenesis and methylotrophic growth

Stasyk, OV., Nazarko, VY., Pochapinsky, OD., Nazarko, TY., Veenhuis, M., Sibirny, AA., Stasyk, O. V., Nazarko, V. Y., Pochapinsky, O. D. & Nazarko, T. Y., Nov-2003, In : Fems Yeast Research. 4, 2, p. 141-147 7 p.

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DOI

  • OV Stasyk
  • VY Nazarko
  • OD Pochapinsky
  • TY Nazarko
  • M Veenhuis
  • AA Sibirny
  • Oleh V. Stasyk
  • Volodymyr Y. Nazarko
  • Olexiy D. Pochapinsky
  • Taras Y. Nazarko

Two interacting AAA ATPases, Pex1p and Pex6p, are indispensable for peroxisome biogenesis in different organisms. Mutations affecting corresponding genes are the most common cause of the peroxisome biogenesis disorders in humans. By UV mutagenesis of the Hansenula polymorpha pex6 mutant, deficient in peroxisome biogenesis, we isolated a conditional cold-sensitive strain with restored ability to grow in methanol medium at 37degreesC but not at 28degreesC. Sequencing of the pex6 allele revealed a point mutation in the first AAA module of the PEX6 gene that leads to substitution of a conserved amino acid residue (G737E). An additional intragenic mutation identified in the cold-sensitive pex6 allele leads to a conserved amino acid substitution in the second AAA domain (R1000G). Electron microscopic analysis revealed restored peroxisomes in methanol-induced cold-sensitive pex6 cells at both permissive and restrictive temperatures. If separated, the secondary mutation did not affect methylotrophic growth. Our data suggest that H. polymorpha Pex6p may have a complex function in peroxisome biogenesis in which identified amino acid residues are involved. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Microbiological Societies.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
JournalFems Yeast Research
Volume4
Issue number2
Publication statusPublished - Nov-2003
Event2nd Hansenula Polymorpha Worldwid Network Conference (HPWN) - , Spain
Duration: 27-Sep-200228-Sep-2002

Event

2nd Hansenula Polymorpha Worldwid Network Conference (HPWN)

27/09/200228/09/2002

Spain

Event: Other

    Keywords

  • peroxisome biogenesis, PEX6, methylotrophic yeast, Hansenula polymorpha, MATRIX PROTEIN IMPORT, DEFICIENT MUTANTS, DISORDERS, ATPASES, FAMILY, INTERACT, SEQUENCE, DISEASE, AAA(+)

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