Effect of deregulation of Sonic Hedgehog pathway on responses to DNA damage and cancer predisposition
Description
The Gorlin syndrome is a rare genetic disorder characterized by several developmental abnormalities. Due to mutations in PTCH1, a key player of the sonic hedgehog signaling pathway, clinical manifestations also includes hyper-radiosensitivity and an increased predisposition to the development of basal cell carcinomas. Given the implication of DNA repair system defects in hyper-radiosensitivity pathologies, we decided to study the effect of PTCH1 mutations on the DNA damage response in order to better understand the cellular and molecular mechanisms leading to Gorlin's phenotype.This study demonstrate a global failure of the DNA damage repair systems in Gorlin fibroblasts with respect to controls. It highlights in particular the collapse of the base excision repair pathway (BER) responsible for the repair of oxidative DNA damage. (author)
Abstract (French)
Le syndrome de Gorlin est une maladie rare caracterisee par de nombreuses anomalies du developpement. Ces manifestations cliniques, dues a des mutations d'un acteur essentiel de la voie de signalisation sonic hedgehog, incluent aussi une hyper-radiosensibilite et une forte predisposition a developper des carcinomes basocellulaires. Etant donne l'implication de defaut de la reparation de l'ADN au niveau des affections liees a l'hyper-radiosensibilite, nous avons decide d'etudier l'effet des mutations du gene PTCH1 sur la reponse aux dommages de l'ADN afin de mieux comprendre les mecanismes cellulaires et moleculaires conduisant au phenotype Gorlin. Cette etude permet de mettre en evidence une defaillance globale des systemes de reparation des dommages de l'ADN dans les fibroblastes issus de patients Gorlin par rapport a des fibroblastes normaux. Elle met notamment en exergue un ecroulement de la reparation par excision de bases (BER) responsable de la reparation des dommages oxydatifs
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Additional details
Additional titles
- Original title (French)
- Effet de la deregulation de la voie Sonic Hedgehog sur les reponses aux dommages de I'ADN et la predisposition aux cancers
Identifiers
Publishing Information
- Imprint Pagination
- 220 p.
- Report number
- FRCEA-TH--8066
INIS
- Country of Publication
- France
- Country of Input or Organization
- France
- INIS RN
- 48031708
- Subject category
- S63: RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS;
- Resource subtype / Literary indicator
- Thesis
- Descriptors DEI
- CARCINOMAS; DNA DAMAGES; DNA REPAIR; EXCISION REPAIR; FIBROBLASTS; MUTATIONS; RADIOSENSITIVITY
- Descriptors DEC
- ANIMAL CELLS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; CONNECTIVE TISSUE CELLS; DISEASES; DNA REPAIR; NEOPLASMS; REPAIR; SENSITIVITY; SOMATIC CELLS
Optional Information
- Notes
- 239 refs.; Available from the INIS Liaison Officer for France, see the 'INIS contacts' section of the INIS-NKM website for current contact and E-mail addresses: http://www.iaea.org/inis/Contacts/; Also available from Bibliotheques Universitaires Grenoble Alpes, scd@ujf-grenoble.fr