(...) In this project we will continue our previously founded SAF-2003-00328 project on the genetics and molecular biology of FA with three major multidisciplinary and interlinked goals: improve our knowledge of the molecular biology and functions of the FA/BRCA pathway, discover new FA proteins and new FA proteins partners and explore the FA/BRCA pathway as a new target in cancer therapy. More specifically, we want to (i) discover the disease gene in a series of FA patients where we have disregarded all currently known FA genes; (ii) dissect the proteomics of FA and of stalled replication forks by pulling down all the partners of FANCD2 and differential proteomics; (iii) prove that the FA/BRCA pathway acts a as negative regulator of telomere length, (iv) investigate the role of the FA/BRCA pathway in centrosome stability and (v) interfere the expression of FA proteins to chemosensitize tumor cells to DNA cross-linking based therapy. To reach these goals. advanced technologies will be employed including genomics (...), differential proteomics (...), analysis of fluorescent-tagged FA proteins in living cells by confocal microscopy and gene knock-down by RNA interference. All the experiments will be done with cells lines and samples currently available in the UAB-Biobank on DNA Repair Syndromes.
|Effective start/end date||1/10/06 → 30/09/09|