Title: Genomic effects of polyamide/DNA interactions on mRNA expression
Authors : Supekova, Lubica
Pezacki, John Paul
Su, Andrew I.
Loweth, Colin J.
Riedl, Rainer
Geierstanger, Bernhard
Schultz, Peter G.
Wemmer, David E.
Published in : Chemistry & Biology
Volume(Issue) : 9
Issue : 7
Pages : 821
Pages to: 827
Publisher / Ed. Institution : Cell Press/Elsevier
Issue Date: 2002
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subjects : Gene chip; Gene expression
Subject (DDC) : 572: Biochemistry
Abstract: Here we characterize the biological activity of a hairpin polyamide 1 that inhibits binding of the minor-groove transcription factor LEF-1, constitutively expressed in colon cancers. Genome-wide analysis of mRNA expression in DLD1 colon cancer cells treated with 1 reveals that a limited number of genes are affected; the most significant changes correspond to genes related to cell cycle, signaling, and proteolysis rather than the anticipated WNT signaling pathway. Treated cells display increased doubling time and hypersensitivity to DNA damage that most likely results from downregulation of DNA-damage checkpoint genes, including YWAE (14-3-3ϵ protein) and DDIT3. Promoter analyses on a genomic level revealed numerous potential polyamide binding sites and multiple possible mechanisms for transcriptional antagonism, underscoring the utility of gene expression profiling in understanding the effects of polyamides on transcription at the cellular level.
Departement: Life Sciences und Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific Journal
DOI : 10.1016/S1074-5521(02)00174-6
ISSN: 1074-5521
2451-9456
URI: https://digitalcollection.zhaw.ch/handle/11475/2856
Appears in Collections:Publikationen Life Sciences und Facility Management

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