Functional characterization of the Caenorhabditis elegans gene fcd-2 during meiosis and in maintenance of genomic stability

Silva, Nicola (2009) Functional characterization of the Caenorhabditis elegans gene fcd-2 during meiosis and in maintenance of genomic stability. [Tesi di dottorato] (Inedito)

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Abstract

Fanconi anemia (FA) is a complex cancer susceptibility disorder associated with defects in the repair of DNA interstrand cross-links (ICLs) resulting in occasional developmental defects and in ICL hypersensitivity of patient cells, yet the precise role of the FA proteins during DNA repair has remained unclear. I will present evidence that FA counteracts illegitimate repair of DNA lesions by non-homologous end joining (NHEJ). FCD-2 has proven to be involved in the choice of repair pathways: 1) fcd-2 mutants show an increase in spo-11 dependent RAD-51 foci and in germline apoptosis, 2) in genetic backgrounds where chiasma formation is abrogated (such as msh-4 and syp-2) resolves in less than the expected 12 DAPI stained bodies at diakinesis, such bodies are the results of chromosome fusions also involving non-homologous chromosomes (as demonstrated by FISH), 4) in the contemporary absence of FCD-2 protein, crossovers and NHEJ (i.e. in the triple mutants fcd-2; syp-2;lig-4 and fcd-2; msh-4;lig-4) we observe more than 12 DAPI stained bodies at diakinesis, a phenotype reminiscent of what observed in brc-1;syp-2 and brc-1;msh-4 double mutants (brc-1 being the ortholog of human BRCA1, see Adamo et al. 2008 enclosed). Furthermore, other fcd-2 mutant phenotypes such as interstrand cross-linking sensitivity and hypermutation are due to promiscuous use of NHEJ.

Tipologia di documento:Tesi di dottorato
Parole chiave:Fanconi anemia, genomic stability, C. elegans
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/18 GENETICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Di Lauro, Robertodilauro@szn.it
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
La Mantia, Girolamalamantia@unina.it
Stato del full text:Accessibile
Data:27 Novembre 2009
Numero di pagine:76
Istituzione:Università degli Studi di Napoli Federico II
Dipartimento o Struttura:Institute of Genetics and Biophysics Adriano Buzzati-Traverso
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Scuola di dottorato:Medicina Molecolare
Denominazione del dottorato:Genetica e Medicina Molecolare
Ciclo di dottorato:XXII
Numero di sistema:3822
Depositato il:19 Maggio 2010 15:51
Ultima modifica:28 Giugno 2012 12:34

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