Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair

Mol Cell. 2012 Feb 10;45(3):371-83. doi: 10.1016/j.molcel.2011.12.028.

Abstract

Homologous recombination (HR) plays an important role in the maintenance of genome integrity. HR repairs broken DNA during S and G2 phases of the cell cycle but its regulatory mechanisms remain elusive. Here, we report that Polo-like kinase 1 (Plk1), which is vital for cell proliferation and is frequently upregulated in cancer cells, phosphorylates the essential Rad51 recombinase at serine 14 (S14) during the cell cycle and in response to DNA damage. Strikingly, S14 phosphorylation licenses subsequent Rad51 phosphorylation at threonine 13 (T13) by casein kinase 2 (CK2), which in turn triggers direct binding to the Nijmegen breakage syndrome gene product, Nbs1. This mechanism facilitates Rad51 recruitment to damage sites, thus enhancing cellular resistance to genotoxic stresses. Our results uncover a role of Plk1 in linking DNA damage recognition with HR repair and suggest a molecular mechanism for cancer development associated with elevated activity of Plk1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • BRCA2 Protein / metabolism
  • Casein Kinase II / metabolism*
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Conserved Sequence
  • DNA Breaks, Double-Stranded*
  • Genomic Instability
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Rad51 Recombinase / chemistry
  • Rad51 Recombinase / metabolism*
  • Recombinational DNA Repair*

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • RAD51 protein, human
  • Rad51 Recombinase