DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). NHEJ is induced by the binding to DSBs of the Ku70-Ku80 heterodimer, which acts as a hub for the recruitment of downstream NHEJ components. An important issue in DSB repair is the maintenance of the DSB ends in close proximity, a function that in yeast involves the MRX complex and Sae2. Here, we provide evidence that Ku contributes to keep the DNA ends tethered to each other. The ku70-C85Y mutation, which increases Ku affinity for DNA and its persistence very close to the DSB ends, enhances DSB end-tethering and suppresses the end-tethering defect of sae2Δ cells. Impairing histone removal around DSBs either by eliminating Tel1 kinase activity or nucleosome remodelers enhances Ku persistence at DSBs and DSB bridging, suggesting that Tel1 antagonizes the Ku function in supporting end-tethering by promoting nucleosome removal and possibly Ku sliding inwards. As Ku provides a block to DSB resection, this Tel1 function can be important to regulate the mode by which DSBs are repaired.

Rinaldi, C., Pizzul, P., Casari, E., Mangiagalli, M., Tisi, R., Longhese, M. (2023). The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase. NUCLEIC ACIDS RESEARCH, 51(4 (28 February 2023)), 1783-1802 [10.1093/nar/gkad062].

The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase

Rinaldi, Carlo
Primo
;
Pizzul, Paolo;Casari, Erika;Mangiagalli, Marco;Tisi, Renata;Longhese, Maria Pia
Ultimo
2023

Abstract

DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). NHEJ is induced by the binding to DSBs of the Ku70-Ku80 heterodimer, which acts as a hub for the recruitment of downstream NHEJ components. An important issue in DSB repair is the maintenance of the DSB ends in close proximity, a function that in yeast involves the MRX complex and Sae2. Here, we provide evidence that Ku contributes to keep the DNA ends tethered to each other. The ku70-C85Y mutation, which increases Ku affinity for DNA and its persistence very close to the DSB ends, enhances DSB end-tethering and suppresses the end-tethering defect of sae2Δ cells. Impairing histone removal around DSBs either by eliminating Tel1 kinase activity or nucleosome remodelers enhances Ku persistence at DSBs and DSB bridging, suggesting that Tel1 antagonizes the Ku function in supporting end-tethering by promoting nucleosome removal and possibly Ku sliding inwards. As Ku provides a block to DSB resection, this Tel1 function can be important to regulate the mode by which DSBs are repaired.
Articolo in rivista - Articolo scientifico
NHEJ, HR, end-tethering, DSBs
English
10-feb-2023
2023
51
4 (28 February 2023)
1783
1802
open
Rinaldi, C., Pizzul, P., Casari, E., Mangiagalli, M., Tisi, R., Longhese, M. (2023). The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase. NUCLEIC ACIDS RESEARCH, 51(4 (28 February 2023)), 1783-1802 [10.1093/nar/gkad062].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/403662
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