Skip to main content
SpringerLink
Log in

Loss of heterozygosity is induced in Candida albicans by ultraviolet irradiation

  • Applied Genetics and Molecular Biotechnology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Candida albicans is a human fungal pathogen and has been extensively studied because of its clinical importance. Comprehensive gene analyses have, however, made little progress. This is because of the diploid and asexual characteristics of the fungus that hamper gene disruptions. In this study, we found that ultraviolet (UV) irradiation, as well as mutagen treatment, strongly stimulated loss of heterozygosity (LOH) in strains harboring artificially constructed heterozygosity. UV-induced LOH occurred more frequently in cells within the logarithmic phase of growth compared to those within the stationary phase of growth. This was observed at all loci tested on chromosome 7, except for a locus neighboring the centromere. C. albicans RAD52, whose orthologue in Saccharomyces cerevisiae was reported to be involved in DNA repair by homologous recombination, was shown to be required for UV-induced LOH. These results suggest that high efficiency LOH caused by UV irradiation could be a prominent tool for gene analyses in C. albicans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Berman J, Sudbery PE (2002) Candida albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet 3(12):918–930

    Article  CAS  Google Scholar 

  • Chibana H, Magee BB, Grindle S, Ran Y, Scherer S, Magee PT (1998) A physical map of chromosome 7 of Candida albicans. Genetics 149(4):1739–1752

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chibana H, Oka N, Nakayama H, Aoyama T, Magee BB, Magee PT, Mikami Y (2005) Sequence finishing and gene mapping for Candida albicans chromosome 7 and syntenic analysis against the Saccharomyces cerevisiae genome. Genetics 170(4):1525–1537

    Article  CAS  Google Scholar 

  • Ciudad T, Andaluz E, Steinberg-Neifach O, Lue NF, Gow NA, Calderone RA, Larriba G (2004) Homologous recombination in Candida albicans: role of CaRad52p in DNA repair, integration of linear DNA fragments and telomere length. Mol Microbiol 53(4):1177–1194

    Article  CAS  Google Scholar 

  • Daigaku Y, Endo K, Watanabe E, Ono T, Yamamoto K (2004) Loss of heterozygosity and DNA damage repair in Saccharomyces cerevisiae. Mutat Res 556(1–2):183–191

    Article  CAS  Google Scholar 

  • Daigaku Y, Mashiko S, Mishiba K, Yamamura S, Ui A, Enomoto T, Yamamoto K (2006) Loss of heterozygosity in yeast can occur by ultraviolet irradiation during the S phase of the cell cycle. Mutat Res 600(1–2):177–183

    Article  CAS  Google Scholar 

  • Dennison PM, Ramsdale M, Manson CL, Brown AJ (2005) Gene disruption in Candida albicans using a synthetic, codon-optimised Cre-loxP system. Fungal Genet Biol 42(9):737–748

    Article  CAS  Google Scholar 

  • Enloe B, Diamond A, Mitchell AP (2000) A single-transformation gene function test in diploid Candida albicans. J Bacteriol 182(20):5730–5736

    Article  CAS  Google Scholar 

  • Fonzi WA, Irwin MY (1993) Isogenic strain construction and gene mapping in Candida albicans. Genetics 134(3):717–728

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hashimoto S, Ogura M, Aritomi K, Hoshida H, Nishizawa Y, Akada R (2005) Isolation of auxotrophic mutants of diploid industrial yeast strains after UV mutagenesis. Appl Environ Microbiol 71(1):312–319

    Article  CAS  Google Scholar 

  • Hiraoka M, Watanabe K, Umezu K, Maki H (2000) Spontaneous loss of heterozygosity in diploid Saccharomyces cerevisiae cells. Genetics 156(4):1531–1548

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hull CM, Raisner RM, Johnson AD (2000) Evidence for mating of the “asexual” yeast Candida albicans in a mammalian host. Science 289(5477):307–310

    Article  CAS  Google Scholar 

  • Kelly R, Miller SM, Kurtz MB, Kirsch DR (1987) Directed mutagenesis in Candida albicans: one-step gene disruption to isolate ura3 mutants. Mol Cell Biol 7(1):199–208

    Article  CAS  Google Scholar 

  • Magee BB, Magee PT (2000) Induction of mating in Candida albicans by construction of MTLa and MTLalpha strains. Science 289(5477):310–313

    Article  CAS  Google Scholar 

  • Noble SM, Johnson AD (2005) Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot Cell 4(2):298–309

    Article  CAS  Google Scholar 

  • Odds FC (1994) Candida albicans, the life and times of a pathogenic yeast. J Med Vet Mycol 32(Suppl 1):1–8

    Article  Google Scholar 

  • Poulter R, Hanrahan V, Jeffery K, Markie D, Shepherd MG, Sullivan PA (1982) Recombination analysis of naturally diploid Candida albicans. J Bacteriol 152(3):969–975

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poulter RT (1987) Natural auxotrophic heterozygosity in Candida albicans. Crit Rev Microbiol 15(1):97–101

    Article  CAS  Google Scholar 

  • Reuss O, Vik A, Kolter R, Morschhauser J (2004) The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341:119–127

    Article  CAS  Google Scholar 

  • Sadhu C, Hoekstra D, McEachern MJ, Reed SI, Hicks JB (1992) A G-protein alpha subunit from asexual Candida albicans functions in the mating signal transduction pathway of Saccharomyces cerevisiae and is regulated by the a1-alpha 2 repressor. Mol Cell Biol 12(5):1977–1985

    Article  CAS  Google Scholar 

  • Sanyal K, Baum M, Carbon J (2004) Centromeric DNA sequences in the pathogenic yeast Candida albicans are all different and unique. Proc Natl Acad Sci U S A 101(31):11374–11379

    Article  CAS  Google Scholar 

  • Sherman F (1991) Getting started with yeast, vol. 194. Academic, San Diego, CA

    Google Scholar 

  • Symington LS (2002) Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev 66(4):630–670

    Article  CAS  Google Scholar 

  • Tsang PW, Cao B, Siu PY, Wang J (1999) Loss of heterozygosity, by mitotic gene conversion and crossing over, causes strain-specific adenine mutants in constitutive diploid Candida albicans. Microbiology 145(Pt 7):1623–1629

    Article  CAS  Google Scholar 

  • Tzung KW, Williams RM, Scherer S, Federspiel N, Jones T, Hansen N, Bivolarevic V, Huizar L, Komp C, Surzycki R, Tamse R, Davis RW, Agabian N (2001) Genomic evidence for a complete sexual cycle in Candida albicans. Proc Natl Acad Sci U S A 98(6):3249–53

    Article  CAS  Google Scholar 

  • Wellington M, Rustchenko E (2005) 5-Fluoro-orotic acid induces chromosome alterations in Candida albicans. Yeast 22(1):57–70

    Article  CAS  Google Scholar 

  • Whelan WL, Magee PT (1981) Natural heterozygosity in Candida albicans. J Bacteriol 145(2):896–903

    Article  CAS  Google Scholar 

  • Whelan WL, Partridge RM, Magee PT (1980) Heterozygosity and segregation in Candida albicans. Mol Gen Genet 180(1):107–113

    Article  CAS  Google Scholar 

  • Wilson RB, Davis D, Enloe BM, Mitchell AP (2000) A recyclable Candida albicans URA3 cassette for PCR product-directed gene disruptions. Yeast 16(1):65–70

    Article  CAS  Google Scholar 

  • Wilson RB, Davis D, Mitchell AP (1999) Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181(6):1868–74

    Article  CAS  Google Scholar 

Download references

Acknowledgment

We thank Suzanne M. Noble for the C. albicans strains and plasmids. This study was supported by a grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan and the New Energy and Industrial Technology Department Organization. Y. Takagi is supported by the Twenty-first Century COE Program of the Ministry of Education, Culture, Sports, Science, and Technology.

Author information

Authors and Affiliations

  1. Division of Integrated Life Sciences, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502, Japan

    Yukinobu Takagi & Kenji Yamamoto

  2. Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Tokiwadai, Ube, 755-8611, Japan

    Rinji Akada

  3. Research Institute of Agricultural Resources, Ishikawa Prefectural University, Nonoichi-cho, Ishikawa, 920-8580, Japan

    Hidehiko Kumagai

  4. Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, Kagoshima, 890-0065, Japan

    Hisanori Tamaki

Authors
  1. Yukinobu Takagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rinji Akada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hidehiko Kumagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenji Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hisanori Tamaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hisanori Tamaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takagi, Y., Akada, R., Kumagai, H. et al. Loss of heterozygosity is induced in Candida albicans by ultraviolet irradiation. Appl Microbiol Biotechnol 77, 1073–1082 (2008). https://doi.org/10.1007/s00253-007-1252-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-007-1252-x

Keywords

Search

Navigation