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Saccharomyces cerevisiae as a model system to study the response to anticancer agents

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

The development of new strategies for cancer therapeutics is indispensable for the improvement of standard protocols and the creation of other possibilities in cancer treatment. Yeast models have been employed to study numerous molecular aspects directly related to cancer development, as well as to determine the genetic contexts associated with anticancer drug sensitivity or resistance. The budding yeast Saccharomyces cerevisiae presents conserved cellular processes with high homology to humans, and it is a rapid, inexpensive and efficient compound screening tool. However, yeast models are still underused in cancer research and for screening of antineoplastic agents. Here, the employment of S. cerevisiae as a model system to anticancer research is discussed and exemplified. Focusing on the important determinants in genomic maintenance and cancer development, including DNA repair, cell cycle control and epigenetics, this review proposes the use of mutant yeast panels to mimic cancer phenotypes, screen and study tumor features and synthetic lethal interactions. Finally, the benefits and limitations of the yeast model are highlighted, as well as the strategies to overcome S. cerevisiae model limitations.

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Abbreviations

5-FU:

5-Fluorouracil

Azacitidine:

5-azacytidine

ATR:

Ataxia telangiectasia and Rad3 related

ATRIP:

ATR-interacting protein

ATM:

Ataxia telangiectasia mutated

BER:

Base excision repair

Decitabine:

5-aza-2′-deoxycytidine

DNMT:

DNA methyl transferase

DSB:

Double-strand break

ET-743:

Ecteinascidin-743

FdUMP:

5-Fluoro-2′-deoxyuridine 5′-monophosphate

HAT:

Histone acetyl transferase

HDAC:

Histone deacetylase

HMGB:

High mobility group box-1

HR:

Homologous recombination

K:

lysine

MMR:

Mismatch repair

MMS:

Methyl methane sulfonate

NER:

Nucleotide excision repair

NHEJ:

Non-homologous end-joining

PARP:

Poli (ADP-ribose) polymerase

PBA:

Sodium phenylbutyrate

PCNA:

Proliferating cell nuclear antigen

PI3K:

Phosphatidylinositol 3-kinase

PRR:

Post-replication repair

RPA:

Replication protein A

SAHA:

Suberoylanilide hydroxamic acid

TLS:

Translesion synthesis

TopBP1:

Topoisomerase-binding protein-1

ssDNA:

Single-strand DNA

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Acknowledgments

We thank Dr. Temenouga N. Guecheva (Departamento de Biofisica da UFRGS) for critically reading the manuscript. This work was supported by research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Biotecnology Center University of Rio Grande do Sul, Fundação de Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/Cofecub (grants No. 583/07) and PRONEX/FAPERGS/CNPq (no. 10/0044-3). Renata Matuo and Fabricio have a fellowship from CNPq and CAPES, respectively, and are graduate students at UFRGS.

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Authors and Affiliations

  1. Departamento de Biofísica, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonçalves, 9500, Prédio 43421, Caixa Postal 15005, Agronomia, Porto Alegre, RS, 91501-970, Brazil

    Renata Matuo, Fabrício G. Sousa, Jenifer Saffi & João Antonio Pêgas Henriques

  2. Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris, France

    Renata Matuo, Fabrício G. Sousa, Daniele G. Soares, Alexandre E. Escargueil & Annette K. Larsen

  3. Institut National de la Santé et de la Recherche Médicale U893, Paris, France

    Renata Matuo, Fabrício G. Sousa, Daniele G. Soares, Alexandre E. Escargueil & Annette K. Larsen

  4. Université Pierre et Marie Curie, UMPC06, Paris, France

    Renata Matuo, Fabrício G. Sousa, Daniele G. Soares, Alexandre E. Escargueil & Annette K. Larsen

  5. Departamento de Biologia Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    Diego Bonatto

  6. Departamento de Ciências Básica da Saúde/Bioquímica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Jenifer Saffi

  7. Departamento de Ciências Biomédicas, Instituto de Biotecnologia, Universidade de Caxias do Sul, UCS, Caxias do Sul, RS, Brazil

    João Antonio Pêgas Henriques

Authors
  1. Renata Matuo
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  2. Fabrício G. Sousa
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  3. Daniele G. Soares
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  4. Diego Bonatto
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  5. Jenifer Saffi
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  6. Alexandre E. Escargueil
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  7. Annette K. Larsen
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  8. João Antonio Pêgas Henriques
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Corresponding author

Correspondence to João Antonio Pêgas Henriques.

Additional information

Renata Matuo and Fabrício G. Sousa contributed equally to this work.

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Matuo, R., Sousa, F.G., Soares, D.G. et al. Saccharomyces cerevisiae as a model system to study the response to anticancer agents. Cancer Chemother Pharmacol 70, 491–502 (2012). https://doi.org/10.1007/s00280-012-1937-4

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  • DOI: https://doi.org/10.1007/s00280-012-1937-4

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