53BP1: A key player of DNA damage response with critical functions in cancer

DNA Repair (Amst). 2019 Jan:73:110-119. doi: 10.1016/j.dnarep.2018.11.008. Epub 2018 Nov 20.

Abstract

Maintenance of genome integrity and stability is a critical responsibility of the DNA damage response (DDR) within cells, such that any disruption in this kinase-based signaling pathway leads to development of various disorders, particularly cancer. The tumor suppressor P53-binding protein 1 (53BP1), as one of the main mediators of DDR, plays a pivotal role in orchestrating the choice of double-strand break (DSB) repair pathway and contains interaction surfaces for numerous DSB-responsive proteins. It has been extensively demonstrated that aberrant expression of 53BP1 contributes to tumor occurrence and development. 53BP1 loss of function in tumor tissues is also related to tumor progression and poor prognosis in human malignancies. Due to undeniable importance of this protein in various aspects of cancer initiation/progression, angiogenesis, metastasis and development of drug resistance, as well as its targeting in the treatment of cancer, this review focused on explaining the structure and function of 53BP1 and its contribution to cancer.

Keywords: 53BP1; Cancer; DNA damage response; DNA repair; Double strand breaks.

Publication types

  • Review

MeSH terms

  • DNA Damage*
  • Genome, Human / genetics
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Signal Transduction
  • Transcription, Genetic
  • Tumor Suppressor p53-Binding Protein 1 / chemistry
  • Tumor Suppressor p53-Binding Protein 1 / genetics
  • Tumor Suppressor p53-Binding Protein 1 / metabolism*

Substances

  • Tumor Suppressor p53-Binding Protein 1