The MRN complex and the cellular response to DNA double-strand breaks The Mre11/Rad50/Nbs1 (MRN) complex is a multisubunit nuclease that plays a crucial role in DNA double-strand break (DSB) repair and ATM (Ataxia-Telangiectasia mutated)-mediated checkpoint signaling. The first part of this thesis addresses the controversy over MRN complex involvement in the non-homologous end-joining (NHEJ) DSB repair pathway by the use of a plasmid DSB repair assay in Xenopus laevis cell-free extracts. Mre11-depleted extracts are able to support efficient NHEJ repair of DSBs, regardless of the end-structure. Mre11-depletion does not alter the kinetics of end-joining or the type and frequency of junctions found in repaired products. Finally, Ku70-independent end-joining events are not affected by Mre11 loss. Our data demonstrate that the MRN complex is not required for efficient and accurate NHEJ-mediated repair of DSBs in this vertebrate system. In the second part, I discuss the techniques, molecular tools and preliminary results of the characterization of the molecular mechanisms underlying the involvement of the MRN-ATM pathway in the maintenance of genome integrity during DNA replication.

The MRN complex and the cellular response to DNA double-strand breaks / M. Di Virgilio ; P. Plevani. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2006. 19. ciclo, Anno Accademico 2005/2006.

The MRN complex and the cellular response to DNA double-strand breaks

M. DI VIRGILIO
2006

Abstract

The MRN complex and the cellular response to DNA double-strand breaks The Mre11/Rad50/Nbs1 (MRN) complex is a multisubunit nuclease that plays a crucial role in DNA double-strand break (DSB) repair and ATM (Ataxia-Telangiectasia mutated)-mediated checkpoint signaling. The first part of this thesis addresses the controversy over MRN complex involvement in the non-homologous end-joining (NHEJ) DSB repair pathway by the use of a plasmid DSB repair assay in Xenopus laevis cell-free extracts. Mre11-depleted extracts are able to support efficient NHEJ repair of DSBs, regardless of the end-structure. Mre11-depletion does not alter the kinetics of end-joining or the type and frequency of junctions found in repaired products. Finally, Ku70-independent end-joining events are not affected by Mre11 loss. Our data demonstrate that the MRN complex is not required for efficient and accurate NHEJ-mediated repair of DSBs in this vertebrate system. In the second part, I discuss the techniques, molecular tools and preliminary results of the characterization of the molecular mechanisms underlying the involvement of the MRN-ATM pathway in the maintenance of genome integrity during DNA replication.
2006
Settore BIO/11 - Biologia Molecolare
PLEVANI, PAOLO
PLEVANI, PAOLO
Doctoral Thesis
The MRN complex and the cellular response to DNA double-strand breaks / M. Di Virgilio ; P. Plevani. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2006. 19. ciclo, Anno Accademico 2005/2006.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/59929
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact