DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences
DNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation vi...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2010-01-01
|
Series: | Journal of Nucleic Acids |
Online Access: | http://dx.doi.org/10.4061/2010/290935 |
id |
doaj-203aa361848d4ff6a6ef12dd6d38ab94 |
---|---|
record_format |
Article |
spelling |
doaj-203aa361848d4ff6a6ef12dd6d38ab942020-11-24T22:02:17ZengHindawi LimitedJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/290935290935DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular ConsequencesGaëlle Lenglet0Marie-Hélène David-Cordonnier1INSERM U-837, Jean-Pierre Aubert Research Center (JPARC), Team 4 Molecular and Cellular Targeting for Cancer Treatment, Institute for Research on Cancer of Lille (IRCL), Lille F-59045, FranceINSERM U-837, Jean-Pierre Aubert Research Center (JPARC), Team 4 Molecular and Cellular Targeting for Cancer Treatment, Institute for Research on Cancer of Lille (IRCL), Lille F-59045, FranceDNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation via tilt, roll, twist, slip, and flip effects. In this ocean of DNA-interacting compounds, most stabilize both DNA strands and very few display helix-destabilizing properties. These types of DNA-destabilizing effect are observed with certain mono- or bis-intercalators and DNA alkylating agents (some of which have been or are being developed as cancer drugs). The formation of locally destabilized DNA portions could interfere with protein/DNA recognition and potentially affect several crucial cellular processes, such as DNA repair, replication, and transcription. The present paper describes the molecular basis of DNA destabilization, the cellular impact on protein recognition, and DNA repair processes and the latter's relationships with antitumour efficacy.http://dx.doi.org/10.4061/2010/290935 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gaëlle Lenglet Marie-Hélène David-Cordonnier |
spellingShingle |
Gaëlle Lenglet Marie-Hélène David-Cordonnier DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences Journal of Nucleic Acids |
author_facet |
Gaëlle Lenglet Marie-Hélène David-Cordonnier |
author_sort |
Gaëlle Lenglet |
title |
DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences |
title_short |
DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences |
title_full |
DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences |
title_fullStr |
DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences |
title_full_unstemmed |
DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences |
title_sort |
dna-destabilizing agents as an alternative approach for targeting dna: mechanisms of action and cellular consequences |
publisher |
Hindawi Limited |
series |
Journal of Nucleic Acids |
issn |
2090-021X |
publishDate |
2010-01-01 |
description |
DNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation via tilt, roll, twist, slip, and flip effects. In this ocean of DNA-interacting compounds, most stabilize both DNA strands and very few display helix-destabilizing properties. These types of DNA-destabilizing effect are observed with certain mono- or bis-intercalators and DNA alkylating agents (some of which have been or are being developed as cancer drugs). The formation of locally destabilized DNA portions could interfere with protein/DNA recognition and potentially affect several crucial cellular processes, such as DNA repair, replication, and transcription. The present paper describes the molecular basis of DNA destabilization, the cellular impact on protein recognition, and DNA repair processes and the latter's relationships with antitumour efficacy. |
url |
http://dx.doi.org/10.4061/2010/290935 |
work_keys_str_mv |
AT gaellelenglet dnadestabilizingagentsasanalternativeapproachfortargetingdnamechanismsofactionandcellularconsequences AT mariehelenedavidcordonnier dnadestabilizingagentsasanalternativeapproachfortargetingdnamechanismsofactionandcellularconsequences |
_version_ |
1725836747778031616 |