Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

FP5

DNA REPAIR DISORDERS Résumé de rapport

Project ID: QLG1-CT-1999-00181
Financé au titre de: FP5-LIFE QUALITY
Pays: United Kingdom

Ultraviolet-sensitive genetic disorders associated with defects in DNA repair and transcription

- We have identified 60 patient mutations in several repair genes.

- Using newly developed immunofluorescence techniques we have been able to visualise, inside the cells, the DNA repair proteins that are defective in XP. During DNA repair, we have been able to determine the order in which these DNA repair proteins are assembled at the sites of DNA damage, and localisation signals responsible for recruiting repair proteins, as well as the dynamics of the repair proteins in real-time.

- We have shown that after UV irradiation, cells are temporarily unable to continue the normal process of transcription. This ability recovers in normal cells but not in cells from patients with CS. We have gained insights into the mechanism of this inhibition.

- We have determined the three-dimensional structure of an important protein TFIIH that is used in both DNA repair and transcription, and shown that in all patients with TTD there are reduced amounts of TFIIH. We have shown that TFIIH is involved in activated transcription.

- We have demonstrated that special enzymes that are required to synthesise DNA past DNA damage are recruited to the sites where DNA is being replicated, and we have discovered how this recruitment takes place. One of these enzymes does not function in a variant form of XP.

-We have generated single and doubly mutant repair-deficient mice, and used them to understand the mechanisms of mutagenesis, carcinogenesis and ageing.

Contact

Alan LEHMANN
Tél.: +44-1273678120
Fax: +44-1273678121
E-mail