Document Detail

Alterations in DNA repair and telomere maintenance mechanism affect response to porphyrins in yeast.
MedLine Citation:
PMID:  11497275     Owner:  NLM     Status:  MEDLINE    
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.
E Izbicka; L D Barnes; A K Robinson; K K Davidson; R A Lawrence; G T Hannibal
Related Documents :
10629035 - The function of dna polymerase alpha at telomeric g tails is important for telomere hom...
20660025 - Telomerase: an rnp enzyme synthesizes dna.
14510465 - Destruction of quadruplex by proteins, and its biological implications in replication a...
19380905 - Telomere maintenance and survival in saccharomyces cerevisiae in the absence of telomer...
18825275 - Inducible sos response system of dna repair and mutagenesis in escherichia coli.
16887575 - An investigation of the prevalence of the toxigenic types of clostridium perfringens in...
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    
Institute for Drug Development, CTRC, San Antonio TX 78245, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antineoplastic Agents / pharmacology
DNA Repair*
Dose-Response Relationship, Drug
Hydroxyurea / pharmacology
Porphyrins / pharmacology*
Saccharomyces cerevisiae / metabolism
Telomere / metabolism*
Grant Support
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

Previous Document:  Tumour cell uptake G2-M accumulation and cytotoxicity of NAMI-A on TS/A adenocarcinoma cells.
Next Document:  Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.