The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal

Karol Kramarz (1) , Kamila Schirmeisen (1) , Virginie Boucherit (1) , Anissia Ait Saada (1) , Claire Lovo (1) , Benoît Palancade (2) , Catherine Freudenreich (3) , Sarah Lambert (1)

1 Intégrité du génome, ARN et cancer
2 IJM (UMR_7592) - Institut Jacques Monod
3 Tufts University [Medford]

Nuclear Pore complexes (NPCs) act as docking sites to anchor particular DNA lesions facilitating DNA repair by elusive mechanisms. Using replication fork barriers in fission yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzymatic activity. The E3 SUMO ligase Pli1 acts at arrested forks to safeguard integrity of nascent strands and generates poly-SUMOylation which promote relocation to NPCs but impede the resumption of DNA synthesis by homologous recombination (HR). Anchorage to NPCs allows SUMO removal by the SENP SUMO protease Ulp1 and the proteasome, promoting timely resumption of DNA synthesis. Preventing Pli1-mediated SUMO chains was sufficient to bypass the need for anchorage to NPCs and the inhibitory effect of poly-SUMOylation on HR-mediated DNA synthesis. Our work establishes a novel spatial control of Recombination-Dependent Replication (RDR) at a unique sequence that is distinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences.

Domaines: Sciences du Vivant [q-bio]

Karol Kramarz, Kamila Schirmeisen, Virginie Boucherit, Anissia Ait Saada, Claire Lovo, et al.. The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-19516-z⟩. ⟨hal-03008915⟩