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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

Role of chromodomain helicase DNA-binding protein 2 in DNA damage response signaling and tumorigenesis

P Nagarajan1, T M Onami, S Rajagopalan

  • 1Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA.

Oncogene
|January 13, 2009
PubMed

Insights

The CHD2 protein is crucial for development, blood formation, and preventing tumors. Chd2 mutant mice show impaired stem cell differentiation and DNA damage response, indicating its role in genome stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Chromodomain helicase DNA-binding proteins (CHDs) regulate gene transcription via chromatin remodeling and histone deacetylation.
  • The specific function of CHD2 in mammalian development and its role in disease remain largely uncharacterized.

Purpose of the Study:

  • To investigate the functional significance of the CHD2 protein in mammals.
  • To elucidate the role of CHD2 in hematopoiesis, tumor suppression, and DNA damage response.

Main Methods:

  • Generation and analysis of a Chd2 mutant mouse model.
  • Assessment of hematopoietic stem cell differentiation and DNA damage response pathways.
  • Evaluation of susceptibility to lymphomagenesis.

Main Results:

  • Chd2 heterozygous mutant mice display increased extramedullary hematopoiesis and heightened susceptibility to lymphomas.
  • Chd2 mutant cells exhibit defects in hematopoietic stem cell differentiation.
  • Mutant cells show elevated levels of gamma H2AX and aberrant DNA damage response following irradiation.

Conclusions:

  • CHD2 plays a critical role in mammalian development, hematopoiesis, and tumor suppression.
  • CHD2 is involved in DNA damage signaling and maintaining genome stability.
  • The chromatin remodeling activity of CHD2 is essential for proper DNA damage response.

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