Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair.
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.
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Keiko
K
Yata
Janette
J
Lloyd
Sarah
S
Maslen
Jean-Yves
JY
Bleuyard
Mark
M
Skehel
Stephen J
SJ
Smerdon
Fumiko
F
Esashi
D000595:Amino Acid Sequence; D024682:BRCA2 Protein / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D053903:DNA Breaks, Double-Stranded; D042822:Genomic Instability; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000737:chemistry / Q000378:metabolism*; D059767:Recombinational DNA Repair; D000097869:Polo-Like Kinase 1
D024682:BRCA2 Protein; D047390:Casein Kinase II; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051135:Rad51 Recombinase; D000097869:Polo-Like Kinase 1; C551750:BRCA2 protein, human; C112156:NBN protein, human; C495153:RAD51 protein, human