RNA:DNA hybrids from Okazaki fragments contribute to establish the Ku-mediated barrier to replication-fork degradation.

Autor:	Audoynaud C; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France., Schirmeisen K; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France., Ait Saada A; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France., Gesnik A; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France., Fernández-Varela P; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France., Boucherit V; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France., Ropars V; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France., Chaudhuri A; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France., Fréon K; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France., Charbonnier JB; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France., Lambert SAE; Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3348, 91400 Orsay, France; Ligue Nationale Contre le cancer (équipe labélisée), Orsay, France. Electronic address: sarah.lambert@curie.fr.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2023 Apr 06; Vol. 83 (7), pp. 1061-1074.e6. Date of Electronic Publication: 2023 Mar 02.
DOI:	10.1016/j.molcel.2023.02.008
Abstrakt:	Nonhomologous end-joining (NHEJ) factors act in replication-fork protection, restart, and repair. Here, we identified a mechanism related to RNA:DNA hybrids to establish the NHEJ factor Ku-mediated barrier to nascent strand degradation in fission yeast. RNase H activities promote nascent strand degradation and replication restart, with a prominent role of RNase H2 in processing RNA:DNA hybrids to overcome the Ku barrier to nascent strand degradation. RNase H2 cooperates with the MRN-Ctp1 axis to sustain cell resistance to replication stress in a Ku-dependent manner. Mechanistically, the need of RNaseH2 in nascent strand degradation requires the primase activity that allows establishing the Ku barrier to Exo1, whereas impairing Okazaki fragment maturation reinforces the Ku barrier. Finally, replication stress induces Ku foci in a primase-dependent manner and favors Ku binding to RNA:DNA hybrids. We propose a function for the RNA:DNA hybrid originating from Okazaki fragments in controlling the Ku barrier specifying nuclease requirement to engage fork resection. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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