Document Detail


Alterations in DNA repair and telomere maintenance mechanism affect response to porphyrins in yeast.
MedLine Citation:
PMID:  11497275     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: DNA quadruplex-interactive porphyrin TMPyP4, but not its isomer TMPyP2, inhibits telomerase activity and causes chromosome fusion in vivo, suggesting interference with telomere maintenance. MATERIALS AND METHODS: We examined effects of these porphyrins and hydroxyurea on growth rates of yeast Saccharomyces cerevisiae wild type and strains with defects in telomere maintenance and/or DNA repair pathways (mec1, tel1, rad9), telomere binding protein (cdc13), and anaphase control (pds1). RESULTS: Hydroxyurea (20 mM) decreased proliferation rates only in mec1 mutant and deletion strains. TMPyP4 (200 microM) decreased growth in all strains, especially in rad9delta and mec1delta. The growth inhibition by TMPyP4 showed low growth inhibition in strains defective in cdc13 and pds1. TMPyP2 sterically prevented from forming a planar species did not significantly inhibit growth of any strain. Overexpression of telomere binding protein Rap1 hypersensitized the mec1delta and tel1delta to TMPyP4. CONCLUSIONS: Telomere maintenance represents a viable target for anticancer agents.
Authors:
E Izbicka; L D Barnes; A K Robinson; K K Davidson; R A Lawrence; G T Hannibal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anticancer research     Volume:  21     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2001 May-Jun
Date Detail:
Created Date:  2001-08-10     Completed Date:  2001-09-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1899-903     Citation Subset:  IM    
Affiliation:
Institute for Drug Development, CTRC, San Antonio TX 78245, USA. eizbicka@saci.org
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
DNA Repair*
Dose-Response Relationship, Drug
Hydroxyurea / pharmacology
Porphyrins / pharmacology*
Saccharomyces cerevisiae / metabolism
Telomere / metabolism*
Grant Support
ID/Acronym/Agency:
CA67760/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Porphyrins; 127-07-1/Hydroxyurea

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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