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

Melissa Leriche, Clara Bonnet, Jagannath Jana, Gita Chhetri, Sabrina Mennour, Sylvain Martineau, Vincent Pennaneach, Didier Busso, Xavier Veaute, Pascale Bertrand, Sarah Lambert, Kumar Somyajit, Patricia Uguen, Stéphan Vagner*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
Article number113412
JournalCell Reports
Volume42
Issue number11
Number of pages14
ISSN2211-1247
DOIs
Publication statusPublished - 28. Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

  • 53BP1
  • CP: Molecular biology
  • DNA replication
  • Okazaki fragments
  • RNA-binding protein

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