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 [Tesi di dottorato] (Unpublished)

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Item Type: Tesi di dottorato
Language: English
Title: Functional characterization of the Caenorhabditis elegans gene fcd-2 during meiosis and in maintenance of genomic stability
Creators:
CreatorsEmail
Silva, Nicolanicola.silva78@gmail.com
Date: 27 November 2009
Number of Pages: 76
Institution: Università degli Studi di Napoli Federico II
Department: Institute of Genetics and Biophysics Adriano Buzzati-Traverso
Doctoral School: Medicina molecolare
PHD name: Genetica e medicina molecolare
PHD cycle: 22
PHD Coordinator:
nameemail
Di Lauro, Robertodilauro@szn.it
Tutor:
nameemail
La Mantia, Girolamalamantia@unina.it
Date: 27 November 2009
Number of Pages: 76
Uncontrolled Keywords: Fanconi anemia, genomic stability, C. elegans
MIUR S.S.D.: Area 05 - Scienze biologiche > BIO/18 - Genetica
Date Deposited: 19 May 2010 13:51
Last Modified: 30 Apr 2014 19:38
URI: http://www.fedoa.unina.it/id/eprint/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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