DNA double-strand breaks (DSBs) are highly hazardous for genome integrity, because failure to repair these lesions can lead to genomic instability. DSBs can arise accidentally at unpredictable locations into the genome, but they are also normal intermediates in meiotic recombination. Moreover, the natural ends of linear chromosomes resemble DSBs. Although intrachromosomal DNA breaks are potent stimulators of the DNA damage response, the natural ends of linear chromosomes are packaged into protective structures called telomeres that suppress DNA repair/recombination activities. Although DSBs and telomeres are functionally different, they both undergo 5'-3' nucleolytic degradation of DNA ends, a process known as resection. The resulting 3'-single-stranded DNA overhangs enable repair of DSBs by homologous recombination (HR), whereas they allow the action of telomerase at telomeres. The molecular activities required for DSB and telomere end resection are similar, indicating that the initial steps of HR and telomerase-mediated elongation are related. Resection of both DSBs and telomeres must be tightly regulated in time and space to ensure genome stability and cell survival.

Longhese, M., Bonetti, D., Manfrini, N., & Clerici, M. (2010). Mechanisms and regulation of DNA end resection. EMBO JOURNAL, 29(17), 2864-2874 [10.1038/emboj.2010.165].

Mechanisms and regulation of DNA end resection

LONGHESE, MARIA PIA
;
BONETTI, DIEGO;MANFRINI, NICOLA;CLERICI, MICHELA
2010

Abstract

DNA double-strand breaks (DSBs) are highly hazardous for genome integrity, because failure to repair these lesions can lead to genomic instability. DSBs can arise accidentally at unpredictable locations into the genome, but they are also normal intermediates in meiotic recombination. Moreover, the natural ends of linear chromosomes resemble DSBs. Although intrachromosomal DNA breaks are potent stimulators of the DNA damage response, the natural ends of linear chromosomes are packaged into protective structures called telomeres that suppress DNA repair/recombination activities. Although DSBs and telomeres are functionally different, they both undergo 5'-3' nucleolytic degradation of DNA ends, a process known as resection. The resulting 3'-single-stranded DNA overhangs enable repair of DSBs by homologous recombination (HR), whereas they allow the action of telomerase at telomeres. The molecular activities required for DSB and telomere end resection are similar, indicating that the initial steps of HR and telomerase-mediated elongation are related. Resection of both DSBs and telomeres must be tightly regulated in time and space to ensure genome stability and cell survival.
Articolo in rivista - Articolo scientifico
Scientifica
checkpoint; double-strand break; meiosis; nucleases; telomere;
English
Longhese, M., Bonetti, D., Manfrini, N., & Clerici, M. (2010). Mechanisms and regulation of DNA end resection. EMBO JOURNAL, 29(17), 2864-2874 [10.1038/emboj.2010.165].
Longhese, M; Bonetti, D; Manfrini, N; Clerici, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/21241
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