MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment

Mol Cancer. 2019 Nov 26;18(1):169. doi: 10.1186/s12943-019-1100-5.

Abstract

Genome instability is a hallmark of cancer cells and can be accelerated by defects in cellular responses to DNA damage. This feature of malignant cells opens new avenues for tumor targeted therapy. MRE11-RAD50-NBS1 complex plays a crucial role in sensing and repair of DNA damage. Through interacting with other important players of DNA damage response, MRE11-RAD50-NBS1 complex is engaged in various DNA damage repair pathways. Mutations in any member of this complex may lead to hypersensitivity to genotoxic agents and predisposition to malignancy. It is assumed that the defects in the complex may contribute to tumorigenesis and that treatments targeting the defect may be beneficial to cancer patients. Here, we summarized the recent research findings of the role of MRE11-RAD50-NBS1 complex in tumorigenesis, cancer treatment and discussed the potential approaches of targeting this complex to treat cancer.

Keywords: DNA damage response; MRN complex; chemotherapy; radiotherapy; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acid Anhydride Hydrolases / metabolism*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • DNA Damage*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • MRE11 Homologue Protein / metabolism*
  • Models, Biological
  • Multiprotein Complexes / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Protein Binding
  • Radiotherapy

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MRE11 protein, human
  • Multiprotein Complexes
  • NBN protein, human
  • Nuclear Proteins
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • RAD50 protein, human