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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Negative cell cycle regulation and DNA damage-inducible phosphorylation of the BRCT protein 53BP1

Z Xia1, J C Morales, W G Dunphy

  • 1Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center, Houston 77030, USA.

The Journal of Biological Chemistry
|October 24, 2000
PubMed

Insights

Researchers discovered X53BP1, a protein involved in DNA damage response. This protein interacts with Xp53 in embryonic cells but not somatic cells, and its function is regulated by ATM kinase.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • 53BP1 is a human BRCT protein known to bind the p53 tumor suppressor.
  • Mitotic catastrophe is a form of programmed cell death that occurs when cells attempt to divide with damaged chromosomes.

Purpose of the Study:

  • To identify suppressors of mitotic catastrophe.
  • To characterize the function and regulation of the Xenopus ortholog of 53BP1 (X53BP1).

Main Methods:

  • Screening for suppressors of mitotic catastrophe.
  • Protein interaction studies using embryonic and somatic cell extracts.
  • Phosphorylation analysis in a DNA damage-dependent manner.
  • In vitro and in vivo kinase assays using ATM kinase.

Main Results:

  • Xenopus 53BP1 (X53BP1) was identified and found to interact with Xp53 in embryonic extracts, but not in somatic cells, suggesting developmental regulation.
  • X53BP1 undergoes DNA damage-dependent phosphorylation, leading to its dispersal into nuclear foci in somatic cells.
  • X53BP1 and its human ortholog are substrates for the ATM kinase, both in vitro and in vivo.

Conclusions:

  • X53BP1 is a novel participant in the DNA damage response pathway.
  • 53BP1 plays a significant role in the DNA damage checkpoint response, potentially in conjunction with ATM.

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