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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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Functional characterization of the Caenorhabditis elegans gene fcd-2 during meiosis and in maintenance of genomic stability
Autori:
AutoreEmail
Silva, Nicolanicola.silva78@gmail.com
Data: 27 Novembre 2009
Numero di pagine: 76
Istituzione: Università degli Studi di Napoli Federico II
Istituzioni (extra): CNR. Istituto di Genetica e Biofisica "Adriano Buzzati-Traverso"
Dipartimento: Biochimica e biotecnologie mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Genetica e medicina molecolare
Ciclo di dottorato: 22
Coordinatore del Corso di dottorato:
nomeemail
Di Lauro, Robertodilauro@szn.it
Tutor:
nomeemail
La Mantia, Girolamalamantia@unina.it
Data: 27 Novembre 2009
Numero di pagine: 76
Parole chiave: Fanconi anemia, genomic stability, C. elegans
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/18 - Genetica
Depositato il: 19 Mag 2010 13:51
Ultima modifica: 21 Gen 2015 11:34
URI: http://www.fedoa.unina.it/id/eprint/3822
DOI: 10.6092/UNINA/FEDOA/3822

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.

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