Relocation of Collapsed Forks to the Nuclear Pore Complex Depends on Sumoylation of DNA Repair Proteins and Permits Rad51 Association.

Jenna M Whalen, Nalini Dhingra, Lei Wei, Xiaolan Zhao, Catherine H Freudenreich

Cell reports 2020 May 12

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Expanded CAG repeats form stem-loop secondary structures that lead to fork stalling and collapse. Previous work has shown that these collapsed forks relocalize to nuclear pore complexes (NPCs) in late S phase in a manner dependent on replication, the nucleoporin Nup84, and the Slx5 protein, which prevents repeat fragility and instability. Here, we show that binding of the Smc5/6 complex to the collapsed fork triggers Mms21-dependent sumoylation of fork-associated DNA repair proteins, and that RPA, Rad52, and Rad59 are the key sumoylation targets that mediate relocation. The SUMO interacting motifs of Slx5 target collapsed forks to the NPC. Notably, Rad51 foci only co-localize with the repeat after it is anchored to the nuclear periphery and Rad51 exclusion from the early collapsed fork is dependent on RPA sumoylation. This pathway may provide a mechanism to constrain recombination at stalled or collapsed forks until it is required for fork restart. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Jenna M Whalen, Nalini Dhingra, Lei Wei, Xiaolan Zhao, Catherine H Freudenreich. Relocation of Collapsed Forks to the Nuclear Pore Complex Depends on Sumoylation of DNA Repair Proteins and Permits Rad51 Association. Cell reports. 2020 May 12;31(6):107635