Rawal et al. identify a non-canonical mechanism of DSB processing in yeast cells lacking the Senataxin ortholog Sen1 helicase, which strictly depends on DNA:RNA hybrid formation at the break and is associated with unfaithful DSB repair and genome instability. An important but still enigmatic function of DNA:RNA hybrids is their role in DNA double-strand break (DSB) repair. Here, we show that Sen1, the budding yeast ortholog of the human helicase Senataxin, is recruited at an HO endonuclease-induced DSB and limits the local accumulation of DNA:RNA hybrids. In the absence of Sen1, hybrid accumulation proximal to the DSB promotes increased binding of the Ku70-80 (KU) complex at the break site, mutagenic non-homologous end joining (NHEJ), micro-homology-mediated end joining (MMEJ), and chromosome translocations. We also show that homology-directed recombination (HDR) by gene conversion is mostly proficient in sen1 mutants after single DSB. However, in the absence of Sen1, DNA:RNA hybrids, Mre11, and Dna2 initiate resection through a non-canonical mechanism. We propose that this resection mechanism through local DNA:RNA hybrids acts as a backup to prime HDR when canonical pathways are altered, but at the expense of genome integrity.
Senataxin Ortholog Sen1 Limits DNA:RNA Hybrid Accumulation at DNA Double-Strand Breaks to Control End Resection and Repair Fidelity / C.C. Rawal, L. Zardoni, M. Di Terlizzi, E. Galati, A. Brambati, F. Lazzaro, G. Liberi, A. Pellicioli. - In: CELL REPORTS. - ISSN 2211-1247. - 31:5(2020 May), pp. 107603.1-107603.8.
|Titolo:||Senataxin Ortholog Sen1 Limits DNA:RNA Hybrid Accumulation at DNA Double-Strand Breaks to Control End Resection and Repair Fidelity|
LIBERI, GIORDANO (Corresponding)
PELLICIOLI, ACHILLE (Ultimo) (Corresponding)
|Parole Chiave:||Dna2; DNA:RNA hybrid; DSB repair; DSB resection; Mre11; Sen1/Senataxin|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||mag-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.celrep.2020.107603|
|Appare nelle tipologie:||01 - Articolo su periodico|