Involvement of 53BP1, a p53 Binding Protein, in Chk2 Phosphorylation of p53 and DNA Damage Cell Cycle Checkpoints

Abstract

We have shown that 53BP1, a tumor suppressor p53 binding proteins, is a key transducer in the DNA damage response signaling. Inhibition of 53BP1 by siRNA in human cancer cell lines resulted in defective S-phase and G2/M checkpoints in response to ionizing irradiation (IR). Mouse embryonic fibroblast (MEF) cells generated from 53BP1 -/- mice were hypersensitive to IR, and displayed a slight G2/M checkpoint deficiency in response to lower dose of IR. We also showed that 53BP1 binds to p53, Chk2 and Brca1. 53BP1 plays an important role in p53 stabilization, phosphorylation of Chk2 and Brca1 in response to IR.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA426338

Entities

People

  • Bin Wang
  • Stephan Elledge

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical And Dental Materials
  • Bone Marrow Cells
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Genetics
  • Immune Serums
  • Lymphatic System
  • Lymphocytes
  • Molecular Biology
  • Polymer Chemistry
  • Proteomics
  • Stem Cells
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and genetic basis of cancer.
  • Nuclear and Radiation Engineering.