Human RAD52 protein regulates homologous recombination and checkpoint function in BRCA2 deficient cells

Int J Biochem Cell Biol. 2019 Feb;107:128-139. doi: 10.1016/j.biocel.2018.12.013. Epub 2018 Dec 24.


Cancer cells exhibit HR defects, increased proliferation and checkpoint aberrations. Tumour suppressor proteins, BRCA2 and p53 counteract such aberrant proliferation by checkpoint regulation. Intriguingly, chemo-resistant cancer cells, exhibiting mutated BRCA2 and p53 protein survive even with increased DNA damage accumulation. Such cancer cells show upregulation of RAD52 tumour suppressor protein implying that RAD52 might be providing survival advantage to cancer cells. To understand this paradoxical condition of a tumour suppressor protein facilitating cancer cell survival, in the current study, we investigate the role of RAD52 overexpression in BRCA2 deficient cells. We provide evidence that RAD52 protein alleviates HR inhibition imposed by p53 in BRCA2 deficient cells. In addition, we study the role of RAD52 protein during short replication stress in BRCA2 deficient cells. BRCA2 deficient cells exhibit excessive origin firing and checkpoint evasion in the presence of prevailing DNA damage. Interestingly, overexpression of RAD52 rescues the excessive origin firing and checkpoint defects observed in BRCA2 deficient cells, indicating RAD52 protein compensates for the loss of BRCA2 function. We show that RAD52 protein, just as BRCA2, interacts with pCHK1 checkpoint protein and helps maintain the checkpoint control in BRCA2 deficient cells during DNA damage response.

Keywords: Cancer; Cell cycle; Homologous recombination; Replication stress; Tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • BRCA2 Protein / deficiency*
  • Cell Line, Tumor
  • DNA Damage
  • DNA Replication
  • Homologous Recombination*
  • Humans
  • Rad52 DNA Repair and Recombination Protein / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • BRCA2 Protein
  • BRCA2 protein, human
  • RAD52 protein, human
  • Rad52 DNA Repair and Recombination Protein
  • Tumor Suppressor Protein p53
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins