DNA repair is essential for maintaining the integrity of the genome. Although mutation often occurs during meiosis and mitosis, the DNA of post-mitotic neurons is also under risk of damage, for example, from free radicals. For humans, given that the lifespan of post-mitotic neurons is many decades, competent DNA repair could be a critical factor in slowing ageing and the progression of some pathologies. Double-strand breaks (DSBs) are considered the most lethal form of DNA damage which, if left unrepaired, can cause cell death. Mammalian cells repair DSBs by two pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). Although in vitro assays support the idea that the mature brain can repair DNA, repair of DSBs has not been directly demonstrated in living post-mitotic neurons. The aim of this study was to test directly the possibility of DSB repair in post-mitotic neurons by using a promoter-less gene-trapping (GT) vector. We found that granule cell primary cultures and cerebellar organotypic slices can integrate and express a promoter-less GT vector, thus revealing DNA repair activity in post-mitotic neurons. Furthermore, we showed that this activity increases after a mild apoptotic stimulus and correlates with an increased expression of both HR and NHEJ DNA repair factors.

DNA repair in post-mitotic neurons: a gene-trapping strategy / D. Merlo; A. M. M. Di Stasi; P. Bonini; C. Mollinari; A. Cardinale; F. Cozzolino; W. Wisden; E. Garaci. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - STAMPA. - 3:(2005), pp. 307-309. [10.1038/sj.cdd.4401572]

DNA repair in post-mitotic neurons: a gene-trapping strategy

COZZOLINO, FEDERICO;
2005

Abstract

DNA repair is essential for maintaining the integrity of the genome. Although mutation often occurs during meiosis and mitosis, the DNA of post-mitotic neurons is also under risk of damage, for example, from free radicals. For humans, given that the lifespan of post-mitotic neurons is many decades, competent DNA repair could be a critical factor in slowing ageing and the progression of some pathologies. Double-strand breaks (DSBs) are considered the most lethal form of DNA damage which, if left unrepaired, can cause cell death. Mammalian cells repair DSBs by two pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). Although in vitro assays support the idea that the mature brain can repair DNA, repair of DSBs has not been directly demonstrated in living post-mitotic neurons. The aim of this study was to test directly the possibility of DSB repair in post-mitotic neurons by using a promoter-less gene-trapping (GT) vector. We found that granule cell primary cultures and cerebellar organotypic slices can integrate and express a promoter-less GT vector, thus revealing DNA repair activity in post-mitotic neurons. Furthermore, we showed that this activity increases after a mild apoptotic stimulus and correlates with an increased expression of both HR and NHEJ DNA repair factors.
2005
3
307
309
D. Merlo; A. M. M. Di Stasi; P. Bonini; C. Mollinari; A. Cardinale; F. Cozzolino; W. Wisden; E. Garaci
File in questo prodotto:
File Dimensione Formato  
DNA repair in post-mitotic neurons a gene-trapping.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 137.17 kB
Formato Adobe PDF
137.17 kB Adobe PDF   Richiedi una copia

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

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/600561
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 22
social impact