Eukaryotic cells preserve genome integrity upon DNA damage by activating a signaling network that promotes DNA repair and controls cell cycle progression. One of the most severe DNA damage is the DNA double-strand break (DSB), whose 5΄ ends can be nucleolitically resected by multiple nucleases to create 3΄-ended single-stranded DNA tails that trigger DSB repair by homologous recombination. Here, we identify the Saccharomyces cerevisiae RNA binding protein Npl3 as a new player in DSB resection. Npl3 is related to both the metazoan serine-arginine-rich and the heterogeneous nuclear ribonucleo-proteins. NPL3 deletion impairs the generation of long ssDNA tails at the DSB ends, whereas it does not exacerbate the resection defect of exo1Δ cells. Furthermore, either the lack of Npl3 or the inactivation of its RNA-binding domains causes decrease of the exonuclease Exo1 protein levels as well as generation of unusual and extended EXO1 RNA species. These findings, together with the observation that EXO1 overexpression partially suppresses the resection defect of npl3Δ cells, indicate that Npl3 participates in DSB resection by promoting the proper biogenesis of EXO1 mRNA

Colombo, C., Trovesi, C., Menin, L., Longhese, M., Clerici, M. (2017). The RNA binding protein Npl3 promotes resection of DNA double-strand breaks by regulating the levels of Exo1. NUCLEIC ACIDS RESEARCH, 45(11), 6530-6545 [10.1093/nar/gkx347].

The RNA binding protein Npl3 promotes resection of DNA double-strand breaks by regulating the levels of Exo1

COLOMBO, CHIARA VITTORIA
Primo
;
TROVESI, CAMILLA
Secondo
;
MENIN, LUCA;LONGHESE, MARIA PIA
Co-ultimo
;
CLERICI, MICHELA
Co-ultimo
2017

Abstract

Eukaryotic cells preserve genome integrity upon DNA damage by activating a signaling network that promotes DNA repair and controls cell cycle progression. One of the most severe DNA damage is the DNA double-strand break (DSB), whose 5΄ ends can be nucleolitically resected by multiple nucleases to create 3΄-ended single-stranded DNA tails that trigger DSB repair by homologous recombination. Here, we identify the Saccharomyces cerevisiae RNA binding protein Npl3 as a new player in DSB resection. Npl3 is related to both the metazoan serine-arginine-rich and the heterogeneous nuclear ribonucleo-proteins. NPL3 deletion impairs the generation of long ssDNA tails at the DSB ends, whereas it does not exacerbate the resection defect of exo1Δ cells. Furthermore, either the lack of Npl3 or the inactivation of its RNA-binding domains causes decrease of the exonuclease Exo1 protein levels as well as generation of unusual and extended EXO1 RNA species. These findings, together with the observation that EXO1 overexpression partially suppresses the resection defect of npl3Δ cells, indicate that Npl3 participates in DSB resection by promoting the proper biogenesis of EXO1 mRNA
Articolo in rivista - Articolo scientifico
Npl3, Exo1, DNA double-strand break, resection, RNA metabolism
English
2-mag-2017
2017
45
11
6530
6545
none
Colombo, C., Trovesi, C., Menin, L., Longhese, M., Clerici, M. (2017). The RNA binding protein Npl3 promotes resection of DNA double-strand breaks by regulating the levels of Exo1. NUCLEIC ACIDS RESEARCH, 45(11), 6530-6545 [10.1093/nar/gkx347].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/151927
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