Expression of human poly (ADP-ribose) polymerase 1 in Saccharomyces cerevisiae: Effect on survival, homologous recombination and identification of genes involved in intracellular localization

Mutation Research
Marco La FerlaA Galli

Abstract

The poly (ADP-ribose) polymerase 1 (PARP-1) actively participates in a series of functions within the cell that include: mitosis, intracellular signaling, cell cycle regulation, transcription and DNA damage repair. Therefore, inhibition of PARP1 has a great potential for use in cancer therapy. As resistance to PARP inhibitors is starting to be observed in patients, thus the function of PARP-1 needs to be studied in depth in order to find new therapeutic targets. To gain more information on the PARP-1 activity, we expressed PARP-1 in yeast and investigated its effect on cell growth and UV induced homologous recombination. To identify candidate genes affecting PARP-1 activity and cellular localization, we also developed a yeast genome wide genetic screen. We found that PARP-1 strongly inhibited yeast growth, but when yeast was exposed to the PARP-1 inhibitor 6(5-H) phenantridinone (PHE), it recovered from the growth suppression. Moreover, we showed that PARP-1 produced PAR products in yeast and we demonstrated that PARP-1 reduced UV-induced homologous recombination. By genome wide screening, we identified 99 mutants that suppressed PARP-1 growth inhibition. Orthologues of human genes were found for 41 of these yeast genes. We det...Continue Reading

References

Aug 1, 1989·Carcinogenesis·R H SchiestlP J Hastings
Apr 1, 1994·The Journal of Cell Biology·R W WozniakM P Rout
Aug 29, 1997·Science·D BotsteinJ M Cherry
Aug 24, 1999·The Biochemical Journal·D D'AmoursG G Poirier
Oct 31, 2000·International Journal of Cancer. Journal International Du Cancer·R MeyerA Bürkle
Jun 18, 2003·Cell·W Lee Kraus, John T Lis
Jun 25, 2003·Molecular Cell·Jessica A DownsStephen P Jackson
Aug 22, 2003·Nucleic Acids Research·Niklas SchultzThomas Helleday
Apr 30, 2005·Trends in Pharmacological Sciences·Willem H Mager, Joris Winderickx
Apr 3, 2007·Nature Protocols·R Daniel Gietz, Robert H Schiestl
Jul 23, 2008·Current Opinion in Pharmacology·Christopher J Lord, Alan Ashworth
Sep 20, 2008·Trends in Biotechnology·Dina Petranovic, Jens Nielsen
Jan 9, 2009·Bioinformatics·Uma MudunuriRobert M Stephens
Jun 13, 2009·Biochimica Et Biophysica Acta·Yi YaoFu-Kun Zhao
Jun 26, 2009·The New England Journal of Medicine·Peter C FongJohann S de Bono
May 14, 2010·Experimental Biology and Medicine·James B Kirkland
Jun 17, 2010·Cancer Research·Ponnari GottipatiThomas Helleday
Jul 28, 2010·Nucleic Acids Research·Alison ClaybonAlexander J R Bishop
Oct 1, 2010·Anti-cancer Agents in Medicinal Chemistry·Anthony J Chalmers
Dec 9, 2010·Nature Biotechnology·Mathias UhlenFredrik Ponten
Feb 9, 2011·Current Problems in Cancer·Marcie K Weil, Alice P Chen
Jun 8, 2011·Nucleic Acids Research·Jüri ReimandJaak Vilo
Nov 8, 2011·Trends in Pharmacological Sciences·Alberto Chiarugi
Nov 16, 2011·Therapeutic Advances in Medical Oncology·M Javle, N J Curtin
Apr 4, 2012·Biochemical Pharmacology·Mike De VosFrançoise Dantzer
Jun 21, 2012·Nature Reviews. Molecular Cell Biology·Bryan A Gibson, W Lee Kraus
Oct 10, 2012·The Journal of Cell Biology·Alex PinesLeon Mullenders
Oct 27, 2012·Cell Cycle·D Gwyn Bebb, Susan P Lees-Miller
Jan 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mihaela RobuGirish M Shah

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.

Breast Cancer: Therapeutic Approaches

Several different therapeutic approaches are used to treat breast cancer. These include chemotherapy, hormonal therapy, targeted therapy, and Immunotherapy. Discover the latest research on breast cancer therapeutic approaches here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Cell Cycle Control & Proteolysis

Key regulators of cell cycle, including cyclins, cyclin dependent kinase inhibitors, DNA replication factors, are controlled by proteolysis. Discover the latest research on cell cycle control and proteolysis.