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Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 4, pp 491–502 | Cite as

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

  • Renata Matuo
  • Fabrício G. Sousa
  • Daniele G. Soares
  • Diego Bonatto
  • Jenifer Saffi
  • Alexandre E. Escargueil
  • Annette K. Larsen
  • João Antonio Pêgas Henriques
Review Article

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.

Keywords

Saccharomyces cerevisiae Anticancer drugs DNA repair Epigenetics Synthetic lethality 

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

Notes

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.

Conflict of interest

None.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Renata Matuo
    • 1
    • 2
    • 3
    • 4
  • Fabrício G. Sousa
    • 1
    • 2
    • 3
    • 4
  • Daniele G. Soares
    • 2
    • 3
    • 4
  • Diego Bonatto
    • 5
  • Jenifer Saffi
    • 1
    • 6
  • Alexandre E. Escargueil
    • 2
    • 3
    • 4
  • Annette K. Larsen
    • 2
    • 3
    • 4
  • João Antonio Pêgas Henriques
    • 1
    • 7
  1. 1.Departamento de Biofísica, Centro de BiotecnologiaUniversidade Federal do Rio Grande do Sul, UFRGSPorto AlegreBrazil
  2. 2.Laboratory of Cancer Biology and TherapeuticsCentre de Recherche Saint-AntoineParisFrance
  3. 3.Institut National de la Santé et de la Recherche Médicale U893ParisFrance
  4. 4.Université Pierre et Marie Curie, UMPC06ParisFrance
  5. 5.Departamento de Biologia Molecular, Centro de BiotecnologiaUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  6. 6.Departamento de Ciências Básica da Saúde/BioquímicaUniversidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil
  7. 7.Departamento de Ciências Biomédicas, Instituto de BiotecnologiaUniversidade de Caxias do Sul, UCSCaxias do SulBrazil

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