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53BP1 interacts with the RNA primer from Okazaki fragments to support their processing during unperturbed DNA
Melissa Leriche1, Clara Bonnet1, Jagannath Jana1
1Institut Curie, PSL Research University, CNRS UMR 3348, INSERM U1278, Orsay, France; Université Paris-Saclay, CNRS UMR 3348, INSERM U1278, Orsay, France; Equipe labellisée Ligue contre le Cancer, Orsay, France.
Cell Reports
|November 14, 2023
Summary
p53-binding protein 1 (53BP1) directly binds to RNA primers on Okazaki fragments during DNA replication. This RNA-binding activity anchors 53BP1 at replication forks, revealing a novel RNA-protein interaction in DNA synthesis.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- RNA-binding proteins (RBPs) are present at replication forks.
- The direct interaction of RBPs with DNA-embedded RNA species is not well understood.
Purpose of the Study:
- To investigate the interaction of p53-binding protein 1 (53BP1) with RNA species at replication forks.
- To determine the role of 53BP1's RNA-binding activity in DNA replication and the stress response.
Main Methods:
- Investigated 53BP1 recruitment to nascent DNA using ribonuclease A treatment.
- Assessed 53BP1 levels in relation to PRIM1 and FEN1 expression.
- Analyzed poly(ADP-ribose) accumulation upon 53BP1 depletion.
Main Results:
- 53BP1 directly interacts with Okazaki fragments, independent of external stress.
- 53BP1 recruitment is dependent on PRIM1 and is enhanced by FEN1 depletion.
- 53BP1 depletion leads to increased poly(ADP-ribose), indicating unligated Okazaki fragments.
Conclusions:
- 53BP1 functions as an RBP that binds to RNA primers at replication forks.
- This RNA-binding activity is crucial for anchoring 53BP1 to nascent DNA.
- Highlights a significant RNA-protein interaction at the DNA replication fork.
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