NUCKS1 promotes RAD54 activity in homologous recombination DNA repair

J Cell Biol. 2020 Oct 5;219(10):e201911049. doi: 10.1083/jcb.201911049.


NUCKS1 (nuclear ubiquitous casein kinase and cyclin-dependent kinase substrate 1) is a chromatin-associated, vertebrate-specific, and multifunctional protein with a role in DNA damage signaling and repair. Previously, we have shown that NUCKS1 helps maintain homologous recombination (HR) DNA repair in human cells and functions as a tumor suppressor in mice. However, the mechanisms by which NUCKS1 positively impacts these processes had remained unclear. Here, we show that NUCKS1 physically and functionally interacts with the DNA motor protein RAD54. Upon exposure of human cells to DNA-damaging agents, NUCKS1 controls the resolution of RAD54 foci. In unperturbed cells, NUCKS1 prevents RAD54's inappropriate engagement with RAD51AP1. In vitro, NUCKS1 stimulates the ATPase activity of RAD54 and the RAD51-RAD54-mediated strand invasion step during displacement loop formation. Taken together, our data demonstrate that the NUCKS1 protein is an important new regulator of the spatiotemporal events in HR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Cell Line
  • DNA-Binding Proteins / genetics*
  • Humans
  • Nuclear Proteins / genetics*
  • Phosphoproteins / genetics*
  • Protein Binding / genetics
  • RNA-Binding Proteins / genetics*
  • Recombinational DNA Repair / genetics*
  • X-linked Nuclear Protein / genetics*


  • DNA-Binding Proteins
  • NUCKS1 protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • RAD51AP1 protein, human
  • RNA-Binding Proteins
  • Adenosine Triphosphatases
  • X-linked Nuclear Protein