DNA Polymerases as Potential Therapeutic Targets for Cancers Deficient in the DNA Mismatch Repair Proteins MSH2 or MLH1
作者： Sarah A. Martin , Nuala McCabe , Michelle Mullarkey , Robert Cummins , Darren J. Burgess
DOI: 10.1016/J.CCR.2009.12.046
关键词:
摘要: Synthetic sickness/lethality (SSL) can be exploited to develop therapeutic strategies for cancer. Deficiencies in the tumor suppressor proteins MLH1 and MSH2 have been implicated Here we demonstrate that deficiency is SSL with inhibition of DNA polymerase POLB, whereas POLG inhibition. Both SSLs led accumulation 8-oxoG oxidative lesions. MSH2/POLB caused nuclear accumulation, MLH1/POLG a rise mitochondrial levels. were rescued by silencing adenine glycosylase MUTYH, suggesting lethality could formation lethal breaks upon accumulation. These data suggest targeted, mechanism-based approaches.
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researchgate.net 参考文章(60)
Lawrence A. Loeb, Raymond J. Monnat, DNA polymerases and human disease Nature Reviews Genetics. ,vol. 9, pp. 594- 604 ,(2008) , 10.1038/NRG2345
Huyong Zheng, Xin Wang, Randy J. Legerski, Peter M. Glazer, Lei Li, Repair of DNA interstrand cross-links: interactions between homology-dependent and homology-independent pathways. DNA Repair. ,vol. 5, pp. 566- 574 ,(2006) , 10.1016/J.DNAREP.2006.01.010
Charles E. Mazzucco, Robert K. Hamatake, Richard J. Colonno, Daniel J. Tenney, Entecavir for Treatment of Hepatitis B Virus Displays No In Vitro Mitochondrial Toxicity or DNA Polymerase Gamma Inhibition Antimicrobial Agents and Chemotherapy. ,vol. 52, pp. 598- 605 ,(2008) , 10.1128/AAC.01122-07
Julie K. Horton, Audrey Baker, Brian J. Vande Berg, Robert W. Sobol, Samuel H. Wilson, Involvement of DNA polymerase β in protection against the cytotoxicity of oxidative DNA damage DNA Repair. ,vol. 1, pp. 317- 333 ,(2002) , 10.1016/S1568-7864(02)00008-3
Qi Wu, Laura A Christensen, Randy J Legerski, Karen M Vasquez, Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells EMBO Reports. ,vol. 6, pp. 551- 557 ,(2005) , 10.1038/SJ.EMBOR.7400418
Youri I Pavlov, Dinh Nguyen, Thomas A Kunkel, Mutator effects of overproducing DNA polymerase η (Rad30) and its catalytically inactive variant in yeast Mutation Research. ,vol. 478, pp. 129- 139 ,(2001) , 10.1016/S0027-5107(01)00131-2
William Lewis, Brian J Day, James J Kohler, Seyed H Hosseini, Sherine S L Chan, Elgin C Green, Chad P Haase, Erin S Keebaugh, Robert Long, Tomika Ludaway, Rodney Russ, Jeffrey Steltzer, Nina Tioleco, Robert Santoianni, William C Copeland, DECREASED mtDNA, OXIDATIVE STRESS, CARDIOMYOPATHY, AND DEATH FROM TRANSGENIC CARDIAC TARGETED HUMAN MUTANT POLYMERASE γ * Laboratory Investigation. ,vol. 87, pp. 326- 335 ,(2007) , 10.1038/LABINVEST.3700523
Helen E. Bryant, Niklas Schultz, Huw D. Thomas, Kayan M. Parker, Dan Flower, Elena Lopez, Suzanne Kyle, Mark Meuth, Nicola J. Curtin, Thomas Helleday, Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Nature. ,vol. 434, pp. 913- 917 ,(2005) , 10.1038/NATURE03443
Y. Mizushina, N. Takahashi, A. Ogawa, K. Tsurugaya, H. Koshino, M. Takemura, S. Yoshida, A. Matsukage, F. Sugawara, K. Sakaguchi, The cyanogenic glucoside, prunasin (D-mandelonitrile-beta-D-glucoside), is a novel inhibitor of DNA polymerase beta. Journal of Biochemistry. ,vol. 126, pp. 430- 436 ,(1999) , 10.1093/OXFORDJOURNALS.JBCHEM.A022468
William G. Kaelin, The Concept of Synthetic Lethality in the Context of Anticancer Therapy Nature Reviews Cancer. ,vol. 5, pp. 689- 698 ,(2005) , 10.1038/NRC1691