Role of Chromodomain Helicase DNA binding protein 2 in DNA damage response signaling and tumorigenesis

The chromodomain helicase DNA binding proteins (CHDs) are known to affect transcription via their ability to remodel chromatin and modulate histone deacetylation. In an effort to understand the functional role of the chromodomain helicase DNA binding protein 2 (CHD2) in mammals, we have generated Chd2 mutant mouse model. Remarkably, the Chd2 protein appears to play a critical role in development, hematopoiesis, and tumor suppression. The Chd2 heterozygous mutant mice exhibit increased extra-medullary hematopoiesis and susceptibility to lymphomas. At the cellular level, Chd2 mutants are defective in hematopoietic stem cell differentiation, accumulate higher levels of the chromatin associated DNA damage response mediator, γH2AX, and exhibit an aberrant DNA damage response after X-ray irradiation. Our data suggest a direct role for the chromatin remodeling protein in DNA damage signaling and genome stability maintenance.