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

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Published on: September 28, 2012

Dynamic changes in nuclear localization of a DNA-binding protein tyrosine phosphatase TCPTP in response to DNA damage

Nadella Kiran Sree1, Ramadhas Anesh, Vegesna Radha

  • 1Drug Discovery, Otsuka Pharma, 9900 Medical Centre Drive, Rockville, MD 20850, USA.

Cell Biology and Toxicology
|September 15, 2012
PubMed

Insights

The tyrosine phosphatase TCPTP (TC45) changes location within cells following DNA damage and replication stress. Its dynamic nuclear localization suggests a role in DNA repair and replication processes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Tyrosine phosphatase TCPTP (TC45) is nuclear, binds DNA, and influences cell cycle G1-S progression.
  • The physiological significance of TCPTP's DNA-binding function remains unclear.
  • Deregulation via overexpression triggers p53-dependent apoptosis.

Purpose of the Study:

  • To investigate how TCPTP localization changes in response to DNA damage and replication arrest.
  • To elucidate the physiological role of TCPTP's DNA-binding function.

Main Methods:

  • Immunocytochemistry and subcellular fractionation were employed.
  • Rat fibroblasts were exposed to UV irradiation and hydroxyurea for replication arrest.
  • Localization changes were assessed via microscopy and protein colocalization studies.

Main Results:

  • UV irradiation increased nuclear-bound TCPTP (TC45), concentrating it in foci colocalizing with PCNA and p53BP1.
  • Replication arrest at G1-S transition caused TCPTP to shift from the nucleus to the cytoplasm.
  • Upon release from arrest, nuclear TCPTP levels increased, coinciding with PCNA and Cdk2 localization.

Conclusions:

  • TCPTP localization is regulated by DNA damage and replication stress.
  • Dynamic changes in TCPTP nuclear localization correlate with PCNA and Cdk2.
  • These findings suggest TCPTP is involved in DNA repair and replication.

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