The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2003. Este documento es privado debido a limitaciones de derechos de autor.

Main Authors: Frisan, Teresa, Cortés Bratti, Ximena, Chaves Olarte, Esteban, Stenerlöw, Bo, Thelestam, Mónica
Format: Artículo
Language: Inglés
Published: Celular Microbiology : 5(10), p. 695-707 2015
Subjects:
Online Access: http://onlinelibrary.wiley.com/doi/10.1046/j.1462-5822.2003.00311.x/abstract
http://hdl.handle.net/10669/13328
id RepoKERWA13328
recordtype dspace
spelling RepoKERWA133282018-06-20T16:58:01Z The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA Frisan, Teresa Cortés Bratti, Ximena Chaves Olarte, Esteban Stenerlöw, Bo Thelestam, Mónica ADN (Citosina-5-) Metiltransferasa Salud pública Genética humana Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2003. Este documento es privado debido a limitaciones de derechos de autor. Among bacterial protein toxins, the cytolethal distending toxins (CDTs) are unique in their ability to activate the DNA damage checkpoint responses, causing cell cycle arrest or apoptosis in intoxicated cells. We provide direct evidence that natural intoxication of cells with the Haemophilus ducreyi CDT (HdCDT) holotoxin induces DNA double-strand breaks similarly to ionizing radiation. Upon DNA damage, epithelial cells and fibroblasts promote the formation of actin stress fibres via activation of the small GTPase RhoA. This phenomenon is not toxin specific, but is part of the ATM-induced cellular responses to genotoxic stresses, including ionizing radiation. Activation of RhoA is associated with prolonged cell survival, as HdCDT-treated epithelial cells expressing a dominant-negative form of RhoA detach and consequently die faster than cells expressing a functional RhoA. Our data highlight several novel aspects of CDT biology: (i) we show that a member of the CDT family causes DNA double-strand breaks in naturally intoxicated cells, acting as a true genotoxic agent; and (ii) we disclose the existence of a novel signalling pathway for intracellularly triggered activation of the RhoA GTPase via the ATM kinase in response to DNA damage, possibly required to prolong cell survival. Universidad de Costa Rica. Instituto de Investigaciones en Salud UCR::Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA) 2015-05-25T21:33:01Z 2015-05-25T21:33:01Z 2003 info:eu-repo/semantics/article Artículo científico http://onlinelibrary.wiley.com/doi/10.1046/j.1462-5822.2003.00311.x/abstract 1462-5814 1462-5822 http://hdl.handle.net/10669/13328 DOI: 10.1046/j.1462-5822.2003.00311.x en_US application/pdf Celular Microbiology : 5(10), p. 695-707 Cellular Microbiology, 2003, 5(10): 695-707
institution Universidad de Costa Rica
collection Repositorio KERWA
language Inglés
topic ADN (Citosina-5-) Metiltransferasa
Salud pública
Genética humana
spellingShingle ADN (Citosina-5-) Metiltransferasa
Salud pública
Genética humana
Frisan, Teresa
Cortés Bratti, Ximena
Chaves Olarte, Esteban
Stenerlöw, Bo
Thelestam, Mónica
The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA
description Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2003. Este documento es privado debido a limitaciones de derechos de autor.
format Artículo
author Frisan, Teresa
Cortés Bratti, Ximena
Chaves Olarte, Esteban
Stenerlöw, Bo
Thelestam, Mónica
author_sort Frisan, Teresa
title The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA
title_short The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA
title_full The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA
title_fullStr The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA
title_full_unstemmed The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA
title_sort haemophilus ducreyi cytolethal distending toxin induces dna double-strand breaks and promotes atm-dependent activation of rhoa
publisher Celular Microbiology : 5(10), p. 695-707
publishDate 2015
url http://onlinelibrary.wiley.com/doi/10.1046/j.1462-5822.2003.00311.x/abstract
http://hdl.handle.net/10669/13328
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score 11.69182