53BP1 interacts with the RNA primer from Okazaki fragments to support their processing during unperturbed DNA replication

RNA-binding proteins (RBPs) are found at replication forks, but their direct interaction with DNA-embedded RNA species remains unexplored. Here, we report that p53-binding protein 1 (53BP1), involved in the DNA damage and replication stress response, is an RBP that directly interacts with Okazaki fr...

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Bibliographic Details
Published in:	Cell reports (Cambridge) Vol. 42; no. 11; p. 113412
Main Authors:	Leriche, Melissa, Bonnet, Clara, Jana, Jagannath, Chhetri, Gita, Mennour, Sabrina, Martineau, Sylvain, Pennaneach, Vincent, Busso, Didier, Veaute, Xavier, Bertrand, Pascale, Lambert, Sarah, Somyajit, Kumar, Uguen, Patricia, Vagner, Stéphan
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 28-11-2023 Elsevier
Subjects:	53BP1 CP: Molecular biology DNA - metabolism DNA replication DNA Replication - genetics Life Sciences Okazaki fragments RNA - genetics RNA - metabolism RNA-binding protein CP: Molecular biology RNA-binding protein DNA replication 53BP1 Okazaki fragments
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Summary:	RNA-binding proteins (RBPs) are found at replication forks, but their direct interaction with DNA-embedded RNA species remains unexplored. Here, we report that p53-binding protein 1 (53BP1), involved in the DNA damage and replication stress response, is an RBP that directly interacts with Okazaki fragments in the absence of external stress. The recruitment of 53BP1 to nascent DNA shows susceptibility to in situ ribonuclease A treatment and is dependent on PRIM1, which synthesizes the RNA primer of Okazaki fragments. Conversely, depletion of FEN1, resulting in the accumulation of uncleaved RNA primers, increases 53BP1 levels at replication forks, suggesting that RNA primers contribute to the recruitment of 53BP1 at the lagging DNA strand. 53BP1 depletion induces an accumulation of S-phase poly(ADP-ribose), which constitutes a sensor of unligated Okazaki fragments. Collectively, our data indicate that 53BP1 is anchored at nascent DNA through its RNA-binding activity, highlighting the role of an RNA-protein interaction at replication forks. [Display omitted] •53BP1 is an RNA-binding protein that directly interacts with RNA-DNA chimeric structures•Perturbation of Okazaki fragment processing changes the proximity of 53BP1 with nascent DNA•Depletion of 53BP1 perturbs the maturation of Okazaki fragments Leriche et al. show that 53BP1, distinct from its canonical mode of recruitment to chromatin, is an RNA-binding protein that interacts with RNA-DNA chimeric structures constituting Okazaki fragments. 53BP1 acts as a binder of Okazaki fragments and plays a role during unstressed DNA replication.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2023.113412